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Aug 12, 2010
 |  BC Innovations  |  Targets & Mechanisms

The GPCR-cancer connection

Researchers from Roche's Genentech Inc.unit have identified a host of somatic mutations and gene copy number alterations across human cancers that represent potential targets for the disease.1 Nineteen of the 112 candidate cancer genes identified are G protein-coupled receptors. With many of these receptors already being targeted in other indications, the path may be open to move rapidly on genes that are validated as cancer targets.

Although previous systematic efforts to sequence somatic mutations in cancer have resulted in new insights into the disease and the identification of new drug targets, these earlier efforts are believed to have only scratched the surface of the cancer genome.2

To expand the list of known somatic mutations, a team led by Somasekar Seshagiri, a senior scientist in molecular biology at Genentech, now has sequenced 1,507 cancer-associated or druggable genes, including 156 G protein-coupled receptors (GPCRs), across 441 human primary tumor samples. These were predominantly breast, lung, ovarian and prostate cancers and subtypes.

A total of 2,567 somatic mutations were identified. Protein-altering mutations occurred in 845 genes, 43% of which had not been previously reported to be mutated in cancer.

"We believe that cataloging changes in tumor genomes is an essential first step in understanding cancer and developing individualized therapeutics to treat it," Seshagiri told SciBX.

Results were published in Nature.

Lynda Chin, a principal investigator for The Cancer Genome Atlas project at the NIH, believes these results complement other cancer genome efforts and confirm "the value of looking broadly and systematically to discover unanticipated genes and insights."

Chin is professor of dermatology at Harvard Medical School and scientific director of the Belfer Institute for Applied Cancer Science and co-leader of the melanoma disease...

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