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Common and Cancer Type-Specific Loss-Of-Heterozygosity in Tumor Stroma and Epithelium of Three Carcinoma Types Associated With Clinical Outcome

Nov. 14, 2008 — A team of researchers led by Charis Eng, M.D., Ph.D., Chair and Director of Cleveland Clinic's Genomic Medicine Institute, has found that in-common genetic alterations in both cancerous cells and the surrounding normal-looking cells (called tumor microenvironment or stroma) play an important role in predicting and dictating the outcome of three cancer types: breast cancer (BC), prostate cancer (CaP) and head neck squamous cell carcinomas (HNSCC).


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The findings not only offer important clues into how a cancer and its micro-environment interact, but show that in-common biomarkers may be important for prognosis among several solid tumor types.

Eng's research team hypothesized that frequent genetic alterations are in-common in BC, CaP and HNSCC, but genetic alterations that are associated with clinicopathological features are unique for specific cancer types. The study analyzed tissue samples from 413 patients and evaluated the cancerous (epithelial) and the surrounding stroma.

The researchers found 15-genetic-marker profiles that were in-common for the three cancer types and are likely to simultaneously predict or explain the cancers. Of these genetic-markers, 11 were stromal-specific, two were epithelial-specific, and two were in both compartments (epithelium and stroma). They also found a genetic-marker that was strongly associated with tumor-grade in CaP and BC only, and another one was associated with nodal metastases in BC and HNSCC only, in both compartments.

"Furthering our understanding of how multiple genetic factors interact between cancer cells and its micro-environment, or stroma, will be a valuable tool for clinicians in predicting how a cancer might spread, as well as forecasting patient outcomes," Eng stated. "Importantly, fewer molecular targets for treatment or prevention across several common carcinomas will facilitate more precise and compartment-specific therapeutic options."

Charis Eng, M.D., Ph.D., is the Director and Chair of the Cleveland Clinic Genomic Medicine Institute, and Professor and Vice Chairman of the Department of Genetics at Case Western Reserve University School of Medicine. Dr. Eng currently serves on the ASHG's Board of Directors. She also serves as Chair of the Clinical Science Committee for the Personalized Medicine Coalition (PMC).

This research was presented at the 58th Annual Meeting of The American Society of Human Genetics (ASHG) in Philadelphia, Pennsylvania on November 11-15, 2008.

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The above story is reprinted from materials provided by American Society of Human Genetics.

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