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The Genomic Basis of Cancer

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  • Title: Research Instructor, Washington University
  • Education: PhD, University of Utah, 1998
  • Recommended by: Rick Wilson

Cancer is a disease of genes and of pathways, says Li Ding, a researcher at the genome center at Washington University in St. Louis. As head of the medical genomics group, Ding works to uncover the genomic changes that lead up to and are associated with human cancer. In particular, she is part of both the Tumor Sequencing Project and the Cancer Genome Atlas efforts. "My research mostly focuses on identifying the genomic alteration associated with human cancer," Ding says.

The TSP is a multicenter collaboration that has a goal of mapping the genomic changes that occur in lung adenocarcinoma, the most common form of lung cancer. The average five-year survival rate for patients with this form of cancer is 15 percent. "The low survival rate is largely due to late-stage detection, so that's why we are interested in studies of this cancer type because of its high overall incidence, in the US and worldwide," Ding says.

The Cancer Genome Atlas project is studying a variety of cancer types: glioblastoma multiforme, ovarian cancer, and squamous cell lung cancer. Some of the findings from the glioblastoma arm of the project were published online in the September 4th edition of Nature. In that study, Ding and her colleagues found three genes — NF1, ERBB2, and PIK3R1 — that are significantly mutated in these tumors that had not previously been associated with the disease. "We're extremely excited about this finding of mutations in the gene called the PIK3R1 because this is the first time that PIK3R1 is identified as a major cancer gene in GBM," she says. Furthermore, she adds, the gene mutations they detected were clustered together in a coding domain that is responsible for interacting with the catalytic domain.

Along the way, Ding has been encouraged by her bosses, Rick Wilson and Elaine Mardis, to follow what interests her. "[Wilson] would always say, 'Go for it! If you think it's interesting, you should dig deeper.' He has always been very supportive," Ding says. For example, as part of the GBM study, Ding saw an interesting feature of the PIK3R1 mutation; Wilson and Mardis suggested looking at more samples even more deeply and going back to older data to figure it out. "They will support you 100 percent," she says.

Looking ahead

Ding says that next-generation sequencing technology will be a boon for determining how cancer arises. These new methods will allow researchers like Ding to screen more genes, more samples, and more types of cancer. "It will allow us [to see] the whole transcriptome, the entire exons of all genes, and the whole genome. It will allow us to look at a large number of tumors for each tumor type," she says. "Eventually [it] will allow us to look at every type of major cancers found in humans and, hopefully, with next-generation sequencing, we can also look into metastasis."

Publications of note

Besides Ding's work with the Cancer Genome Atlas project, she has also published a number of papers dealing with her work on lung adenocarcinomas. In a Cancer Research paper that came out this past July, Ding and her colleagues identified a novel MEK1 mutation in the EGFR signaling pathway of lung adenocarcinomas.

And the Nobel goes to …

Ding's end goal is to improve patient care. "If we can develop something that can help treatment of cancer, any type of human cancer, I think that would be my dream," she says.

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