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Kornelia Polyak, MD, PhD

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Kornelia Polyak, MD, PhD

Researcher

  • Professor of Medicine, Harvard Medical School

Contact Information

  • Office Phone Number617-632-2106
  • Fax617-580-8490

Bio

Dr. Polyak obtained her M.D. degree in 1991 from the Albert Szent-Györgyi Medical School in Szeged Hungary and her Ph.D. degree in 1995 from Cornell University Graduate School of Medical Sciences/Sloan-Kettering Cancer Center, New York. Dr. Polyak completed her postdoctoral training in Baltimore at the Johns Hopkins Oncology Center in the laboratory of Drs. Bert Vogelstein and Ken Kinzler. Dr. Polyak joined the faculty of Dana-Farber Cancer Institute and Harvard Medical School in 1998 as Assistant Professor of Medicine and was promoted to Professor in 2011. Dr. Polyak’s laboratory is dedicated to the molecular analysis of human breast cancer with the goal improving the clinical management of breast cancer patients. Her lab has devoted much effort to develop new ways to study tumors as a whole and to apply interdisciplinary approaches. Using these methods Dr. Polyak’s lab has been at the forefront of studies analyzing purified cell populations from normal and neoplastic human breast tissue at genomic scale and in situ at single cell level and to apply mathematical and ecological models for the better understanding of breast tumor evolution. She has also been successful with the clinical translation of her findings including the testing of efficacy of JAK2 and BET bromodomain inhibitors for the treatment of triple-negative breast cancer in clinical trials. Dr. Polyak have received numerous awards including the Paul Marks Prize for Cancer Research in 2011, the 2012 AACR Outstanding Investigator Award for Breast Cancer Research, and the Rosalind Franklin Award in 2016. She is also a 2015 recipient of the NCI Outstanding Investigator award.

Recent Awards:

  • 14th Rosalind E. Franklin Award for Women in Science, NIH, 2016
  • Outstanding Investigator Award, NCI 2015
  • AACR Outstanding Investigator Award for Breast Cancer Research, San Antonio, TX 2012
  • Paul Marks Award for Cancer Research, Sloan-Kettering Cancer Center, New York, NY 2011
  • Elected to the Johns Hopkins Society of Scholars 2008
  • 27th Annual Award for Outstanding Achievement in Cancer Research, American Association for Cancer Research 2007
  • Claire W. and Richard P. Morse Research Award, Dana-Farber Cancer Institute 2006
  • Tisch Family Outstanding Achievement Award, Dana-Farber Cancer Institute 2005
  • V Foundation Scholar Award 2001
  • Sidney Kimmel Scholar Award 1999

Research

Molecular Basis of Breast Tumor Evolution
Research in my laboratory is dedicated to the molecular analysis of human breast cancer. Our goal is to identify differences between normal and cancerous breast tissue, determine their consequences, and use this information to improve the clinical management of breast cancer patients. The three main areas of our interests are: (1) how to accurately predict breast cancer risk and prevent breast cancer initiation or progression from in situ to invasive disease, (2) better understand drivers of tumor evolution with special emphasis on metastatic progression and therapeutic resistance, and (3) novel therapeutic targets in breast cancer with particular focus on “bad” cancers such as triple-negative breast cancer and inflammatory breast cancer. All of our studies start with analyzing samples from breast cancer patients (or normal healthy women for the risk studies), formulate hypotheses based on our observations, use experimental models to test these, and then translate back our findings into clinical care.
Highlights from our breast cancer risk and prevention study: The highest impact on breast cancer-associated morbidity and mortality will be achieved with two tools.  The first tool is a test that accurately predicts an individual’s risk of developing breast cancer. This will allow us to identify who needs preventive action and who does not.  Second, is to discover the best agent for prevention that will be universally effective.  We know that inheriting mutated BRCA1 and BRCA2 genes confer a high risk of breast cancer, and the most effective prevention strategy currently available is prophylactic oophorectomy and mastectomy. Other significant determinants of breast cancer risk are reproductive history and mammographic density. Epidemiological data suggest that pregnancy induces long-lasting effects in the normal breast, except in BRCA1 and BRCA2 mutation carriers, where pregnancy does not decrease breast cancer risk.
What cells need to be eliminated in the breast to reduce risk?  A number of studies have shown that breast epithelial progenitor cells are the likely the “cell-of-origin” of breast cancer. It stands to reason then, that eliminating them will abolish tumor development. In recent work we analyzed and characterized multiple cell types from normal breast tissues of nulliparous and parous women, including BRCA1 and BRCA2 mutation carriers. We detected the most significant differences in breast epithelial progenitors and found that the frequency of these cells is higher in women with higher risk of breast cancer. We have also identified key signaling pathways important for their proliferation and showed that by modulating the activity of these pathways we can decrease the frequency of the progenitor cells, thus, potentially reducing breast cancer risk. We propose that the progenitor markers identified can be used for breast cancer risk prediction and that depleting these progenitors will decrease the risk of breast cancer. We are pursuing these studies in large cohorts in women and in rodent models of breast cancer (prevention) with immediate plans to translate our findings to high risk women as the drugs used to deplete these progenitors are already in clinical trials for cancer treatment.
Highlights from our cancer heterogeneity studies: With rare exceptions tumors are thought to originate from a single cell. Yet, at the time of diagnosis the majority of human tumors display startling heterogeneity in many structural and physiological features, such as cell size, shape, metastatic proclivity, and sensitivity to therapy. This diversity within tumors (intratumor) complicates the study and treatment of cancer because small tumor samples may not be representative of the whole tumor and because a treatment that targets one tumor cell population, may not affect another, leading to a poor clinical response. On the positive side, intratumor diversity is a type of “looking glass” for a particular cancer from which we can both learn its past and predict its future.
Until recently, mainstream cancer research has been focusing on the identification and therapeutic targeting of “cancer-driving” genetic alterations.  However, recent large-scale sequencing of breast cancer genomes has been disappointing and identified relatively few recurrent mutations that could be explored for therapy. In addition, most of the mutations were detected only in a subset of tumors and at a low frequency, making it difficult to determine their relevance in tumorigenesis. The outcome of these sequencing studies reinforced the already high interest in intratumor heterogeneity. Intratumor heterogeneity for heritable traits is a fundamental challenge in breast cancer, underlying disease progression and treatment resistance. Yet our understanding of its mechanisms, and as a consequence, our ability to control it remains limited. This is largely due to the cancer-gene and cancer cell-focus of mainstream cancer research and the reliance on experimental models that poorly reproduce this key aspect of the human disease.
We have developed a model of intratumor clonal (i.e., group of cells with common ancestry) heterogeneity in breast cancer and utilized this to assess the functional relevance of clonal interactions in metastatic progression. We found that polyclonal tumors were commonly metastatic, even though none of the individual clones present in them showed this behavior in monoclonal tumors. We have also analyzed breast tumor samples before and after pre-operative chemotherapy, or at different stages of disease progression (i.e., primary and metastatic lesions) for the degree of intratumor genetic and phenotypic heterogeneity at the single cell level. We found that tumors with the lowest pretreatment genetic diversity responded the best to treatment and that distant metastatic lesions had higher genetic diversity compared to primary tumors and lymph node metastases. Lastly, we have developed mathematical models based on these experimental data that can infer the evolution of tumors during treatment. Based on these data, we hypothesize that intratumor heterogeneity per se is a driver of metastatic spread and therapeutic resistance. Thus, measures of intratumor heterogeneity can be used to predict the risk of metastasis and to personalize therapy based on this. At the same time, understanding of how heterogeneity within tumors promotes disease progression may reveal new therapeutic targets and would allow us to design more effective and individualized treatment strategies.
Bacterial Darth Vader: May the force be with you. Cancer Cell. 2022 06 13; 40(6):600-602.
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Report of the First International Symposium on NUT Carcinoma. Clin Cancer Res. 2022 06 13; 28(12):2493-2505.
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Insights into Immune Escape During Tumor Evolution and Response to Immunotherapy Using a Rat Model of Breast Cancer. Cancer Immunol Res. 2022 06 03; 10(6):680-697.
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Inhibition of EZH2 transactivation function sensitizes solid tumors to genotoxic stress. Proc Natl Acad Sci U S A. 2022 01 18; 119(3).
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A Darwinian perspective on tumor immune evasion. Biochim Biophys Acta Rev Cancer. 2022 01; 1877(1):188671.
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The MCF10 Model of Breast Tumor Progression. Cancer Res. 2021 08 15; 81(16):4183-4185.
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The impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2+ breast cancer. JCI Insight. 2021 06 08; 6(11).
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Early-Life Body Adiposity and the Breast Tumor Transcriptome. J Natl Cancer Inst. 2021 06 01; 113(6):778-784.
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Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab. Cancer Discov. 2021 10; 11(10):2474-2487.
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Identifying key questions in the ecology and evolution of cancer. Evol Appl. 2021 Apr; 14(4):877-892.
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Genomic Alterations during the In Situ to Invasive Ductal Breast Carcinoma Transition Shaped by the Immune System. Mol Cancer Res. 2021 04; 19(4):623-635.
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Increased lysosomal biomass is responsible for the resistance of triple-negative breast cancers to CDK4/6 inhibition. Sci Adv. 2020 06; 6(25):eabb2210.
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Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Mol Cell. 2020 06 18; 78(6):1096-1113.e8.
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Acquired resistance to combined BET and CDK4/6 inhibition in triple-negative breast cancer. Nat Commun. 2020 05 11; 11(1):2350.
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Intratumor Heterogeneity: The Rosetta Stone of Therapy Resistance. Cancer Cell. 2020 04 13; 37(4):471-484.
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Premenopausal Plasma Osteoprotegerin and Breast Cancer Risk: A Case-Control Analysis Nested within the Nurses' Health Study II. Cancer Epidemiol Biomarkers Prev. 2020 06; 29(6):1264-1270.
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Immune Escape during Breast Tumor Progression. Cancer Immunol Res. 2020 04; 8(4):422-427.
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A roadmap for the next decade in cancer research. Nat Cancer. 2020 01; 1(1):12-17.
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Tumor Neoantigens: When Too Much of a Good Thing Is Bad. Cancer Cell. 2019 11 11; 36(5):466-467.
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Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ. Nat Commun. 2019 09 13; 10(1):4182.
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Subclonal cooperation drives metastasis by modulating local and systemic immune microenvironments. Nat Cell Biol. 2019 07; 21(7):879-888.
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EN1 Is a Transcriptional Dependency in Triple-Negative Breast Cancer Associated with Brain Metastasis. Cancer Res. 2019 08 15; 79(16):4173-4183.
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Metastasis as a systemic disease: molecular insights and clinical implications. Biochim Biophys Acta Rev Cancer. 2019 08; 1872(1):89-102.
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Intratumoral Heterogeneity: More Than Just Mutations. Trends Cell Biol. 2019 07; 29(7):569-579.
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Deletion of Cdkn1b in ACI rats leads to increased proliferation and pregnancy-associated changes in the mammary gland due to perturbed systemic endocrine environment. PLoS Genet. 2019 03; 15(3):e1008002.
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KDM5 Histone Demethylase Activity Links Cellular Transcriptomic Heterogeneity to Therapeutic Resistance. Cancer Cell. 2019 Feb 11; 35(2):330-332.
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Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment. Cancer Discov. 2019 02; 9(2):176-198.
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Epidemiology, Biology, Treatment, and Prevention of Ductal Carcinoma In Situ (DCIS). JNCI Cancer Spectr. 2018 Nov; 2(4):pky063.
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KDM5 Histone Demethylase Activity Links Cellular Transcriptomic Heterogeneity to Therapeutic Resistance. Cancer Cell. 2018 12 10; 34(6):939-953.e9.
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TRPS1 Is a Lineage-Specific Transcriptional Dependency in Breast Cancer. Cell Rep. 2018 10 30; 25(5):1255-1267.e5.
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Intratumor heterogeneity defines treatment-resistant HER2+ breast tumors. Mol Oncol. 2018 11; 12(11):1838-1855.
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Dissecting the mammary gland one cell at a time. Nat Commun. 2018 06 26; 9(1):2473.
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A confetti trail of tumour evolution. Nat Cell Biol. 2018 06; 20(6):639-641.
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Phase II study of ruxolitinib, a selective JAK1/2 inhibitor, in patients with metastatic triple-negative breast cancer. NPJ Breast Cancer. 2018; 4:10.
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Myoepithelial cell-specific expression of stefin A as a suppressor of early breast cancer invasion. J Pathol. 2017 12; 243(4):496-509.
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Scientific Summary from the Morgan Welch MD Anderson Cancer Center Inflammatory Breast Cancer (IBC) Program 10th Anniversary Conference. J Cancer. 2017; 8(17):3607-3614.
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Classifying the evolutionary and ecological features of neoplasms. Nat Rev Cancer. 2017 10; 17(10):605-619.
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Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition. Cancer Discov. 2017 10; 7(10):1098-1115.
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The metabolic function of cyclin D3-CDK6 kinase in cancer cell survival. Nature. 2017 06 15; 546(7658):426-430.
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Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers. Cancer Cell. 2017 04 10; 31(4):576-590.e8.
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Precancer Atlas to Drive Precision Prevention Trials. Cancer Res. 2017 04 01; 77(7):1510-1541.
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Mathematical Modeling Links Pregnancy-Associated Changes and Breast Cancer Risk. Cancer Res. 2017 06 01; 77(11):2800-2809.
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G1 cyclins link proliferation, pluripotency and differentiation of embryonic stem cells. Nat Cell Biol. 2017 03; 19(3):177-188.
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BET Bromodomain Proteins as Cancer Therapeutic Targets. Cold Spring Harb Symp Quant Biol. 2016; 81:123-129.
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Expression of estrogen receptor, progesterone receptor, and Ki67 in normal breast tissue in relation to subsequent risk of breast cancer. NPJ Breast Cancer. 2016; 2.
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Spatial Proximity to Fibroblasts Impacts Molecular Features and Therapeutic Sensitivity of Breast Cancer Cells Influencing Clinical Outcomes. Cancer Res. 2016 11 15; 76(22):6495-6506.
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Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer. Cell Rep. 2016 08 16; 16(7):2032-46.
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BRCA1/FANCD2/BRG1-Driven DNA Repair Stabilizes the Differentiation State of Human Mammary Epithelial Cells. Mol Cell. 2016 07 21; 63(2):277-292.
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The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women. Cancer Res. 2016 04 01; 76(7):1926-34.
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Voices of biotech. Nat Biotechnol. 2016 Mar; 34(3):270-5.
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Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature. 2016 Jan 21; 529(7586):413-417.
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Intratumor Heterogeneity in Breast Cancer. Adv Exp Med Biol. 2016; 882:169-89.
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Principles Governing A-to-I RNA Editing in the Breast Cancer Transcriptome. Cell Rep. 2015 Oct 13; 13(2):277-89.
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Combining miR-10b-Targeted Nanotherapy with Low-Dose Doxorubicin Elicits Durable Regressions of Metastatic Breast Cancer. Cancer Res. 2015 Oct 15; 75(20):4407-15.
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In situ single-cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2-positive breast cancer. Nat Genet. 2015 Oct; 47(10):1212-9.
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Toward understanding and exploiting tumor heterogeneity. Nat Med. 2015 Aug; 21(8):846-53.
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HOXB7 Is an ERa Cofactor in the Activation of HER2 and Multiple ER Target Genes Leading to Endocrine Resistance. Cancer Discov. 2015 Sep; 5(9):944-59.
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Tumorigenesis: it takes a village. Nat Rev Cancer. 2015 Aug; 15(8):473-83.
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Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer. Cell Rep. 2015 Jun 16; 11(10):1549-63.
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Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling. BMC Cancer. 2015 Feb 19; 15:70.
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CLK2 Is an Oncogenic Kinase and Splicing Regulator in Breast Cancer. Cancer Res. 2015 Apr 01; 75(7):1516-26.
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Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells. Stem Cell Reports. 2015 Feb 10; 4(2):297-311.
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Clonal evolution in cancer: a tale of twisted twines. Cell Stem Cell. 2015 Jan 08; 16(1):11-2.
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BRCA1 haploinsufficiency for replication stress suppression in primary cells. Nat Commun. 2014 Nov 17; 5:5496.
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MSC-regulated microRNAs converge on the transcription factor FOXP2 and promote breast cancer metastasis. Cell Stem Cell. 2014 Dec 04; 15(6):762-74.
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Tumor heterogeneity: the Lernaean hydra of oncology? Oncology (Williston Park). 2014 Sep; 28(9):781-2, 784.
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Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity. Nature. 2014 Oct 02; 514(7520):54-8.
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JARID1B is a luminal lineage-driving oncogene in breast cancer. Cancer Cell. 2014 Jun 16; 25(6):762-77.
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Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes. J Biol Chem. 2014 Jun 20; 289(25):17620-33.
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Oncogene-like induction of cellular invasion from centrosome amplification. Nature. 2014 Jun 05; 510(7503):167-71.
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Cancer: Clonal cooperation. Nature. 2014 Apr 03; 508(7494):52-3.
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Tumor heterogeneity confounds and illuminates: a case for Darwinian tumor evolution. Nat Med. 2014 Apr; 20(4):344-6.
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Sorting out the FACS: a devil in the details. Cell Rep. 2014 Mar 13; 6(5):779-81.
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Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell Rep. 2014 Feb 13; 6(3):514-27.
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Genetic and phenotypic diversity in breast tumor metastases. Cancer Res. 2014 Mar 01; 74(5):1338-48.
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Targeting Akt3 signaling in triple-negative breast cancer. Cancer Res. 2014 Feb 01; 74(3):964-73.
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Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell. 2013 Oct 14; 24(4):450-65.
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The RasGAP gene, RASAL2, is a tumor and metastasis suppressor. Cancer Cell. 2013 Sep 09; 24(3):365-78.
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Methylation-specific digital karyotyping of HPV16E6E7-expressing human keratinocytes identifies novel methylation events in cervical carcinogenesis. J Pathol. 2013 Sep; 231(1):53-62.
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Molecular profiling of human mammary gland links breast cancer risk to a p27(+) cell population with progenitor characteristics. Cell Stem Cell. 2013 Jul 03; 13(1):117-30.
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Tracking tumor resistance using 'liquid biopsies'. Nat Med. 2013 Jun; 19(6):676-7.
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Deconvoluting complex tissues for expression quantitative trait locus-based analyses. Philos Trans R Soc Lond B Biol Sci. 2013; 368(1620):20120363.
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Cancer. Cancer cell phenotypes, in fifty shades of grey. Science. 2013 Feb 01; 339(6119):528-9.
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RNA sequencing of cancer reveals novel splicing alterations. Sci Rep. 2013; 3:1689.
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The expression of Psoriasin (S100A7) and CD24 is linked and related to the differentiation of mammary epithelial cells. PLoS One. 2012; 7(12):e53119.
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A blueprint for an international cancer epigenome consortium. A report from the AACR Cancer Epigenome Task Force. Cancer Res. 2012 Dec 15; 72(24):6319-24.
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Cellular heterogeneity and molecular evolution in cancer. Annu Rev Pathol. 2013 Jan 24; 8:277-302.
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SnapShot: breast cancer. Cancer Cell. 2012 Oct 16; 22(4):562-562.e1.
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The challenges posed by cancer heterogeneity. Nat Biotechnol. 2012 Jul 10; 30(7):604-10.
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On using functional genetics to understand breast cancer biology. Cold Spring Harb Perspect Biol. 2012 Jul 01; 4(7):a013516.
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Sequence analysis of mutations and translocations across breast cancer subtypes. Nature. 2012 Jun 20; 486(7403):405-9.
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Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer. 2012 Apr 19; 12(5):323-34.
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Evolutionary pathways in BRCA1-associated breast tumors. Cancer Discov. 2012 Jun; 2(6):503-11.
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On chromatin remodeling in mammary gland differentiation and breast tumorigenesis. Cold Spring Harb Perspect Biol. 2012 Mar 01; 4(3).
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Progress in breast cancer research. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):2715-7.
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Somatic mutations in the Notch, NF-KB, PIK3CA, and Hedgehog pathways in human breast cancers. Genes Chromosomes Cancer. 2012 May; 51(5):480-9.
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The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium. Proc Natl Acad Sci U S A. 2012 Jan 03; 109(1):221-6.
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PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling. Oncogene. 2012 Jul 19; 31(29):3397-408.
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The microenvironment in breast cancer progression: biology and implications for treatment. Breast Cancer Res. 2011; 13(6):227.
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Heterogeneity in breast cancer. J Clin Invest. 2011 Oct; 121(10):3786-8.
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Unraveling the complexity of basal-like breast cancer. Oncotarget. 2011 Aug; 2(8):588-9.
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The JAK2/STAT3 signaling pathway is required for growth of CD44?CD24? stem cell-like breast cancer cells in human tumors. J Clin Invest. 2011 Jul; 121(7):2723-35.
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Epigenetic regulation of cell type-specific expression patterns in the human mammary epithelium. PLoS Genet. 2011 Apr; 7(4):e1001369.
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Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc Natl Acad Sci U S A. 2011 May 10; 108(19):7950-5.
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Functional synergies yet distinct modulators affected by genetic alterations in common human cancers. Cancer Res. 2011 May 15; 71(10):3471-81.
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Targeting the missing links for cancer therapy. Nat Med. 2011 Mar; 17(3):283-4.
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Altered antisense-to-sense transcript ratios in breast cancer. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):2820-4.
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Gene expression profiling of human breast tissue samples using SAGE-Seq. Genome Res. 2010 Dec; 20(12):1730-9.
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The origins and implications of intratumor heterogeneity. Cancer Prev Res (Phila). 2010 Nov; 3(11):1361-4.
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Going small is the new big. Nat Methods. 2010 Aug; 7(8):597, 599-600.
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PTK6 regulates IGF-1-induced anchorage-independent survival. PLoS One. 2010 Jul 23; 5(7):e11729.
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The role of the microenvironment in mammary gland development and cancer. Cold Spring Harb Perspect Biol. 2010 Nov; 2(11):a003244.
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PIK3CA mutations in in situ and invasive breast carcinomas. Cancer Res. 2010 Jul 15; 70(14):5674-8.
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Stem cells in the human breast. Cold Spring Harb Perspect Biol. 2010 May; 2(5):a003160.
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Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res. 2010 Feb 01; 16(3):876-87.
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Knock in of the AKT1 E17K mutation in human breast epithelial cells does not recapitulate oncogenic PIK3CA mutations. Oncogene. 2010 Apr 22; 29(16):2337-45.
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Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype. J Clin Invest. 2010 Feb; 120(2):636-44.
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Molecular markers for the diagnosis and management of ductal carcinoma in situ. J Natl Cancer Inst Monogr. 2010; 2010(41):210-3.
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Profiling critical cancer gene mutations in clinical tumor samples. PLoS One. 2009 Nov 18; 4(11):e7887.
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Tumor heterogeneity: causes and consequences. Biochim Biophys Acta. 2010 Jan; 1805(1):105-17.
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Control of cyclin D1 and breast tumorigenesis by the EglN2 prolyl hydroxylase. Cancer Cell. 2009 Nov 06; 16(5):413-24.
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Clonal mutations in the cancer-associated fibroblasts: the case against genetic coevolution. Cancer Res. 2009 Sep 01; 69(17):6765-8; discussion 6769.
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Identification of CD44v6(+)/CD24- breast carcinoma cells in primary human tumors by quantum dot-conjugated antibodies. Lab Invest. 2009 Aug; 89(8):857-66.
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Epigenetic patterns of embryonic and adult stem cells. Cell Cycle. 2009 Mar 15; 8(6):809-17.
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Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009 Apr; 9(4):265-73.
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Origin of carcinoma associated fibroblasts. Cell Cycle. 2009 Feb 15; 8(4):589-95.
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Role of COX-2 in epithelial-stromal cell interactions and progression of ductal carcinoma in situ of the breast. Proc Natl Acad Sci U S A. 2009 Mar 03; 106(9):3372-7.
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Cancer stem cells: a model in the making. Curr Opin Genet Dev. 2009 Feb; 19(1):44-50.
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An intraductal human-in-mouse transplantation model mimics the subtypes of ductal carcinoma in situ. Breast Cancer Res. 2009; 11(5):R66.
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Co-evolution of tumor cells and their microenvironment. Trends Genet. 2009 Jan; 25(1):30-8.
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Molecular characterisation of the tumour microenvironment in breast cancer. Eur J Cancer. 2008 Dec; 44(18):2760-5.
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Genome-wide functional synergy between amplified and mutated genes in human breast cancer. Cancer Res. 2008 Nov 15; 68(22):9532-40.
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Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9. Breast Cancer Res. 2008; 10(5):R91.
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Detection of psoriasin/S100A7 in the sera of patients with psoriasis. Br J Dermatol. 2009 Feb; 160(2):325-32.
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Cell type-specific DNA methylation patterns in the human breast. Proc Natl Acad Sci U S A. 2008 Sep 16; 105(37):14076-81.
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Epithelial and stromal cathepsin K and CXCL14 expression in breast tumor progression. Clin Cancer Res. 2008 Sep 01; 14(17):5357-67.
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The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008 May 16; 133(4):704-15.
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Regulation of in situ to invasive breast carcinoma transition. Cancer Cell. 2008 May; 13(5):394-406.
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No evidence of clonal somatic genetic alterations in cancer-associated fibroblasts from human breast and ovarian carcinomas. Nat Genet. 2008 May; 40(5):650-5.
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Breast-cancer stromal cells with TP53 mutations. N Engl J Med. 2008 Apr 10; 358(15):1634-5; author reply 1636.
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The cancer stem cell hypothesis: in search of definitions, markers, and relevance. Lab Invest. 2008 May; 88(5):459-63.
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S100A7-downregulation inhibits epidermal growth factor-induced signaling in breast cancer cells and blocks osteoclast formation. PLoS One. 2008 Mar 05; 3(3):e1741.
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Microenvironmental regulation of cancer development. Curr Opin Genet Dev. 2008 Feb; 18(1):27-34.
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Cyclooxygenase-2 expression during immortalization and breast cancer progression. Cancer Res. 2008 Jan 15; 68(2):467-75.
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Is breast tumor progression really linear? Clin Cancer Res. 2008 Jan 15; 14(2):339-41.
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Breast cancer: origins and evolution. J Clin Invest. 2007 Nov; 117(11):3155-63.
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The genomic landscapes of human breast and colorectal cancers. Science. 2007 Nov 16; 318(5853):1108-13.
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Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007 Oct 04; 449(7162):557-63.
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Serial analysis of gene expression (SAGE): experimental method and data analysis. Curr Protoc Mol Biol. 2007 Oct; Chapter 25:Unit 25B.6.
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Breast tumor heterogeneity: cancer stem cells or clonal evolution? Cell Cycle. 2007 Oct 01; 6(19):2332-8.
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Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell. 2007 Jun 15; 129(6):1065-79.
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Breast cancer stem cells: a case of mistaken identity? Stem Cell Rev. 2007 Jun; 3(2):107-9.
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Serial analysis of gene expression (SAGE): experimental method and data analysis. Curr Protoc Hum Genet. 2007 Apr; Chapter 11:Unit 11.7.
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Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007 Mar; 11(3):259-73.
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The p27Kip1 tumor suppressor gene: Still a suspect or proven guilty? Cancer Cell. 2006 Nov; 10(5):352-4.
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Combined cDNA array comparative genomic hybridization and serial analysis of gene expression analysis of breast tumor progression. Cancer Res. 2006 Apr 15; 66(8):4065-78.
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Pregnancy and breast cancer: the other side of the coin. Cancer Cell. 2006 Mar; 9(3):151-3.
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Roots and stems: stem cells in cancer. Nat Med. 2006 Mar; 12(3):296-300.
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SAGE and related approaches for cancer target identification. Drug Discov Today. 2006 Feb; 11(3-4):110-8.
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Methylation-specific digital karyotyping. Nat Protoc. 2006; 1(3):1621-36.
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Serial analysis of gene expression. Nat Protoc. 2006; 1(4):1743-60.
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A putative role for psoriasin in breast tumor progression. Cancer Res. 2005 Dec 15; 65(24):11326-34.
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HIN-1, an inhibitor of cell growth, invasion, and AKT activation. Cancer Res. 2005 Nov 01; 65(21):9659-69.
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Psoriasin (S100A7) and calgranulin-B (S100A9) induction is dependent on reactive oxygen species and is downregulated by Bcl-2 and antioxidants. Cancer Biol Ther. 2005 Sep; 4(9):998-1005.
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Distinct epigenetic changes in the stromal cells of breast cancers. Nat Genet. 2005 Aug; 37(8):899-905.
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Do myoepithelial cells hold the key for breast tumor progression? J Mammary Gland Biol Neoplasia. 2005 Jul; 10(3):231-47.
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Contribution of bone marrow-derived endothelial cells to human tumor vasculature. Nat Med. 2005 Mar; 11(3):261-2.
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Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types. Mol Cancer Res. 2004 Sep; 2(9):489-94.
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Cancer chromosomes in crisis. Nat Genet. 2004 Sep; 36(9):932-4.
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EMSY links breast cancer gene 2 to the 'Royal Family'. Breast Cancer Res. 2004; 6(5):201-3.
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Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell. 2004 Jul; 6(1):17-32.
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Very high frequency of hypermethylated genes in breast cancer metastasis to the bone, brain, and lung. Clin Cancer Res. 2004 May 01; 10(9):3104-9.
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Ductal carcinoma in situ of the breast. N Engl J Med. 2004 Apr 01; 350(14):1430-41.
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Estrogen receptor/progesterone receptor-negative breast cancers of young African-American women have a higher frequency of methylation of multiple genes than those of Caucasian women. Clin Cancer Res. 2004 Mar 15; 10(6):2052-7.
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DNA methylation of RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma. Int J Cancer. 2003 Dec 20; 107(6):970-5.
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Cancer target discovery using SAGE. Expert Opin Ther Targets. 2003 Dec; 7(6):759-69.
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A neural survival factor is a candidate oncogene in breast cancer. Proc Natl Acad Sci U S A. 2003 Sep 16; 100(19):10931-6.
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The hairy powers of oncogenes: from biological function to cancer therapy. Cancer Biol Ther. 2003 Sep-Oct; 2(5):592-4.
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Identifying tumor origin using a gene expression-based classification map. Cancer Res. 2003 Jul 15; 63(14):4144-9.
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Lack of HIN-1 methylation in BRCA1-linked and "BRCA1-like" breast tumors. Cancer Res. 2003 May 01; 63(9):2024-7.
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Molecular markers in ductal carcinoma in situ of the breast. Mol Cancer Res. 2003 Mar; 1(5):362-75.
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Breast cancer gene discovery. Expert Rev Mol Med. 2002 Aug 15; 4(18):1-18.
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Cellular and molecular targets of estrogen in normal human breast tissue. Cancer Res. 2002 Aug 15; 62(16):4540-4.
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An anatomy of normal and malignant gene expression. Proc Natl Acad Sci U S A. 2002 Aug 20; 99(17):11287-92.
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Expression of high in normal-1 (HIN-1) and uteroglobin related protein-1 (UGRP-1) in adult and developing tissues. Mech Dev. 2002 Jun; 114(1-2):201-4.
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Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression). Oncogene. 2002 Jan 24; 21(5):836-43.
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Molecular alterations in ductal carcinoma in situ of the breast. Curr Opin Oncol. 2002 Jan; 14(1):92-6.
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Is p53 a breast cancer gene? Cancer Biol Ther. 2002 Jan-Feb; 1(1):37-8.
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Psoriasin expression in mammary epithelial cells in vitro and in vivo. Cancer Res. 2002 Jan 01; 62(1):43-7.
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On the birth of breast cancer. Biochim Biophys Acta. 2001 Nov 30; 1552(1):1-13.
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A SAGE (serial analysis of gene expression) view of breast tumor progression. Cancer Res. 2001 Aug 01; 61(15):5697-702.
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HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells. Proc Natl Acad Sci U S A. 2001 Aug 14; 98(17):9796-801.
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Gene discovery using the serial analysis of gene expression technique: implications for cancer research. J Clin Oncol. 2001 Jun 01; 19(11):2948-58.
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Phenol sulfotransferases: hormonal regulation, polymorphism, and age of onset of breast cancer. Cancer Res. 2000 Dec 15; 60(24):6859-63.
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p53-dependent expression of PIG3 during proliferation, genotoxic stress, and reversible growth arrest. Cancer Lett. 2000 Aug 01; 156(1):63-72.
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Analysis of human transcriptomes. Nat Genet. 1999 Dec; 23(4):387-8.
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A public database for gene expression in human cancers. Cancer Res. 1999 Nov 01; 59(21):5403-7.
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CDX2 is mutated in a colorectal cancer with normal APC/beta-catenin signaling. Oncogene. 1999 Sep 02; 18(35):5010-4.
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Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet. 1998 Nov; 20(3):291-3.
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Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A. 1998 Jun 09; 95(12):6870-5.
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14-3-3sigma is a p53-regulated inhibitor of G2/M progression. Mol Cell. 1997 Dec; 1(1):3-11.
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A model for p53-induced apoptosis. Nature. 1997 Sep 18; 389(6648):300-5.
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Less death in the dying. Cell Death Differ. 1997 Apr; 4(3):242-6.
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Early alteration of cell-cycle-regulated gene expression in colorectal neoplasia. Am J Pathol. 1996 Aug; 149(2):381-7.
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Genetic determinants of p53-induced apoptosis and growth arrest. Genes Dev. 1996 Aug 01; 10(15):1945-52.
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A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice. Cell. 1996 May 31; 85(5):733-44.
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Negative regulation of cell growth by TGF beta. Biochim Biophys Acta. 1996 Mar 18; 1242(3):185-99.
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Expression of the human mismatch repair gene hMSH2 in normal and neoplastic tissues. Cancer Res. 1996 Jan 15; 56(2):235-40.
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Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta. Genes Dev. 1995 Aug 01; 9(15):1831-45.
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Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature. 1995 Jul 27; 376(6538):313-20.
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p27Kip1: chromosomal mapping to 12p12-12p13.1 and absence of mutations in human tumors. Cancer Res. 1995 Mar 15; 55(6):1211-4.
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Mammalian antiproliferative signals and their targets. Curr Opin Genet Dev. 1995 Feb; 5(1):91-6.
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p27KIP1, an inhibitor of cyclin-dependent kinases. Prog Cell Cycle Res. 1995; 1:141-7.
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Interleukin-2-mediated elimination of the p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin. Nature. 1994 Dec 08; 372(6506):570-3.
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Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation. Cell. 1994 Nov 04; 79(3):487-96.
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Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell. 1994 Jul 15; 78(1):59-66.
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Cyclins, Cdks, and cyclin kinase inhibitors. Cold Spring Harb Symp Quant Biol. 1994; 59:31-8.
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p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev. 1994 Jan; 8(1):9-22.
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Negative regulation of G1 in mammalian cells: inhibition of cyclin E-dependent kinase by TGF-beta. Science. 1993 Apr 23; 260(5107):536-9.
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  • Myles A. Brown, MD
    News Releases
    5/12/2020

    Three Dana-Farber faculty members elected as Fellows of The American Association for Cancer Research

    Kornelia Polyak, MD, PhD
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    11/26/2019

    Dana-Farber Cancer Institute Faculty named AAAS 2019 Fellows

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