UNC Lineberger scientists lead definition of key lung cancer genome

Study opens doors to better, more targeted therapies

UNC Lineberger scientists lead definition of key lung cancer genome click to enlarge Neil Hayes, MD, MPH

Media contact: Dianne G. Shaw, 919-966-7834, dgs@med.unc.edu

Sunday, Sept. 9, 2012

CHAPEL HILL, N.C. - In the September 9, 2012 early online edition of Nature, scientists with The Cancer Genome Atlas (TCGA) report that they have characterized the lung squamous cell carcinoma genome.

Squamous cell carcinoma is the second most common form of lung cancer, a disease that kills more Americans than any other type of cancer.

The national team of scientists examined tumor samples from 178 patients with untreated lung squamous cell carcinoma and completed genetic analysis of the tumors, work that paves the way for developing better, more targeted therapies to treat the cancer.

Neil Hayes, MD, MPH, a UNC investigator with TCGA, explains, “The work confirms the prevalence of commonly known cancer genes such as p53 and p16 in LSCC: alteration of p53 in patients is approaching 100 percent while 70-80 percent of patients have clear alterations of p16. Our report documents a long list of mutations that could be targeted therapeutically, some even now with drugs currently available or in clinical trials.”

Dr. Hayes served as co-chair of the manuscript writing committee for the paper. With Matthew Wilkerson, PhD, he served as genomic analysis leader and mRNA sequence analysis. Dr. Hayes is an associate professor of medicine.

He says, “UNC scientists generated all of the microarray and sequencing data on RNA and provided technical expertise in analyzing it. Analyzing gene expression data is very challenging, and UNC brought a large number of collaborators in computer science, statistics, and genetics to help.

“We and all TCGA scientists worked closely together on all aspects of this work,” he explains. “Participating institutions provided high-quality tumor samples for the analysis. The study required a wide range of technical expertise to perform all the assays, and no one center could have done it all. “

Putting the study in a scientific context, he explains, “This is like a lot of great science advances.  Think back to the late 1700s before it was widely known that many diseases were caused by infections. It’s very hard to consider the idea of an antibiotic until you’ve thought of a germ. We have a disease that’s caused by alterations in DNA. It’s hard to think about therapies until you know what’s wrong with the DNA. In the case of lung cancer, we’ve made a huge step forward in understanding what’s wrong with the DNA of lung cancer.”

Co-PI Charles Perou, PhD, says, “This, and other TCGA studies show the powers of a multi-institutional and multi-technological approach. For LSCC, we not only studied the tumor DNA, but also the tumor RNA, with the integration of these data types yielded far more information that either type alone. These data identified numerous new and old drug targets, which is setting the stage for the next generation of clinical trials for LSCC patients.” Dr. Perou is the May Goldman Shaw Distinguished Professor of Molecular Oncology.

TCGA is a groundbreaking effort to sequence the entire genome of 20 individual cancers, involving scientists from around the world.  UNC Lineberger was one of the original consortium members and will receive over $20 million in grants to fund the research, which extends across multiple types of cancer.  TCGA is funded jointly by the National Cancer Institute and the National Human Genome Research Institute, both part of the National Institutes of Health.

Other UNC co-authors on the paper are: Todd Auman, PhD; Katherine Hoadley, PhD; Yan Shi, PhD; Christina Liquori, PhD; Shaowu Meng, PhD; Ling Li, MS ; Yidi Turman, BS ;Michael Topal, PhD; Donghui Tan, MS ; Scot Waring, PhD; Elizabeth Buda, MS; Jesse Walsh, MS; Corbin Jones, PhD; Piotr Mieczkowski, PhD; Darshan Singh, MS; Junyuan W, MSu, ; Anisha Gulabani, BS: Peter Dolina, MS; Tom Bodenheimer,MS ;Alan Hoyle, BS; Janae Simons,BS, ; Matthew Solaway, BS; Lisle Mose, MS; Stuart Jeffreys, PhD; Saianand Balu, MS; Brian O’Connor, PhD; Jan Prins, PhD; Jinze Liu, PhD; and Derek Chiang, PhD.

This work was supported by the following grants from the NIH: U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544, U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA126563, U24CA143840, U24CA143882, U24CA143731, U24CA143835, U24CA143845, U24CA143858, U24CA144025, U24CA143882, U24CA143866, U24CA143867, U24CA143848, U24CA143843 and R21CA135877 and supplemented by the Recovery Act.

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