Genomics

OncoMap: Profiling Tumor DNA

Matthew Meyerson, MD, PhD (left), and Levi Garraway, MD, PhD, with the robotic nanodispenser 

In a laboratory bay on the 15th floor of the Dana building, a robotic nanodispenser hums mechanically in the background as a mass spectrometer churns out genotyping data. Though mass spectrometric genotyping has typically been used to find single nucleotide polymorphisms in germline DNA, researchers at Dana-Farber are applying the technology to ferret out known point mutations in tumor DNA for which targeted therapies already exist or are in development. This novel screening approach, called OncoMap, is the brainchild of physician-scientist Levi Garraway, MD, PhD, of the Department of Medical Oncology and a member of the Center for Cancer Genome Discovery, who developed the technique in collaboration with the Broad Institute.

Garraway, who specialized in tropical parasites for his PhD, never planned to become a cancer researcher. But as an MD/PhD student, he faced a career crossroads when his scientist father was suddenly diagnosed with prostate cancer. "Since that day," says Garraway, "the guiding theme of my career has been translating molecular and genetic understanding of cancer into the clinic."

Following a research fellowship at Dana-Farber, Garraway joined the faculty in 2005, started his own lab, and began searching for a cost-effective way to profile mutations in many different tumor types. "We realized, in principle, that we could adapt mass spectrometric genotyping to extract highly relevant information from tumors that might guide therapy choices and yet cost only pennies per genetic variant," says Garraway. Still, demonstrating the value of the OncoMap approach was another matter. He and colleagues, including Matthew Meyerson, MD, PhD, of Medical Oncology, initially tested the technology by scouring cancer DNA for 238 known mutations in 17 oncogenes. Their work culminated in a "eureka" moment as the first wave of data streamed off the robots, transforming principle into reality. "We were observing mutations in tumor types we would never have expected, a priori," says Garraway. "It was an exceedingly satisfying moment." With the addition of institutional resources for large-scale mutation profiling, OncoMap has now expanded into numerous other scientific and clinical research projects. "By systematically profiling diverse tumor collections for critical mutations, we hope to enable definitive advances in molecular oncology and, ultimately, to promote personalized cancer medicine," says Garraway.