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Nicholas Navin: The Evolution of Cancer Tumors

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Education: PhD, Stony Brook University, 2010
Recommended By: Elaine Mardis, Washington University in St. Louis

Sometimes you have to think small to think big. As a PhD student, Nicholas Navin found himself thinking of cancer in a new way — instead of studying tumor samples from many different people at the same time, he could instead chose to focus on many cells from the same tumor. Based on the idea of tumor heterogeneity, Navin hypothesized that he could compare different cells and order them to infer the tumor's lineage and deduce how its mutations progressed.

When he conducted a study using mostly copy-number arrays, Navin found himself stumped by a problem — the samples contained millions of cells and there was too much admixture. But when he applied his approach to several tumors, he found an interesting trend. "Instead of a gradual pattern of evolution where mutations keep accumulating, the evolution of a tumor is very punctuated, kind of like the fossil record," Navin says. "We also found within the normal cells of tumors that there was a population of cells that underwent random deletions of chromosomes and gains of chromosomes and represent this apparent process where a lot of diversity generates into a tumor."

Navin is now interested in figuring out how tumors will continue to evolve by reconstructing the evolution that has already occurred. Most researchers who study tumor progression will gather a large cohort of subjects and sample them once, he says. But the problem is that individual patients' tumors can travel down different mutational pathways, and only high-frequency events are identified when they are only sampled once. "Our idea was to take an individual tumor and then try to sample it hundreds of times and try to understand the mutational pathway that occurs in each specific case," Navin says.

Papers of note

In the June issue of Molecular Oncology, Navin discusses two established approaches to trace a tumor's lineage and how these approaches can best be used to interpret current models of tumor progression. "Recent technical advances in single-cell genomics will improve our understanding of the fundamental basis of tumor heterogeneity and progression," Navin et al. wrote.

And the Nobel goes to ...

Navin says it "would be nice" to win the Nobel Prize for his contributions to the cancer field, particularly for changing how researchers look at tumors. "Instead of thinking of it as one homogenous organ, maybe people could think of it more as an evolutionary population that can vary in different regions and can also change in response to therapies," Navin says. "Perhaps that could improve patient treatment."

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