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Study Reveals Large Number of Cancer Genes
A systematic study of a gene family commonly associated with cancer has implicated a much larger repertoire of cancer genes than researchers had anticipated.
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| A large-scale DNA sequencing center. Image courtesy of the Cancer Genome Atlas project. |
“Cancer” is the term for cells that are growing uncontrolled. They often arise from mutations in genes that confer a growth advantage on the cells that harbor them. More than 350 cancer genes have thus far been identified.
Genes for a family of proteins called kinases, which regulate other proteins in the cell, are the most common among known cancer genes. Inhibitors of mutated protein kinases have recently shown promise in cancer treatment. Dr. Christopher Greenman at the Wellcome Trust Sanger Institute and his colleagues therefore set out to survey the numbers and patterns of kinase gene mutations in a diverse set of human cancers. Their studies were funded by NIH’s National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI), along with the Wellcome Trust.
As they reported in the March 8, 2007, edition of Nature, the researchers extracted DNA from 210 human cancers, including breast, lung, colorectal, gastric, testis, ovarian, renal, melanoma, glioma and acute lymphoblastic leukemia. They then sequenced all the 518 known protein kinase genes in each sample and searched the DNA sequences for mutations. While 73 of the cancers had no mutations in these genes, others had many. In all, they found 1,007 mutations, about a third of which had been previously reported.
Using statistical analysis, the researchers estimated that 158 of the mutations, distributed in 119 of the protein kinase genes, were “drivers” for cancer. Sixty-six of the 210 samples contained one of these mutations, implicating mutated protein kinase genes in the development of about a third of the cancers studied.
The research team’s systematic sequencing of cancer genomes revealed a considerably larger evolutionary diversity of cancers and repertoire of cancer genes than many had anticipated. The researchers say that the full range of mutation patterns likely won’t become apparent until thousands of cancer samples have been sequenced. NIH has proposed the Cancer Genome Atlas Project to accelerate genome analysis technologies, such as the ones used in this study, to better understand the molecular basis of cancer. This study’s encouraging results show that the strategy may yield important and unexpected results.
— by Harrison Wein, Ph.D.
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