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Genetic Errors Identified in 12 Major Cancer Types

By BiotechDaily International staff writers
Posted on 07 Nov 2013
Image: Immunohistochemistry of paraffin-embedded human ovary tumor using P53 antibody (Photo courtesy of Proteintech).
Image: Immunohistochemistry of paraffin-embedded human ovary tumor using P53 antibody (Photo courtesy of Proteintech).
The latest sequencing and analysis methods have been used to identify somatic variants across thousands of tumors, and 127 significantly mutated genes were detected.

Some of the same genes commonly mutated in certain cancers also occur in seemingly unrelated tumors. For example, a gene mutated in 25% of leukemia cases in the study also was found in tumors of the breast, rectum, head and neck, kidney, lung, ovary and uterus.

Scientists at the Washington University School of Medicine (St. Louis, MO, USA) performed exome sequencing on thousands of tumor samples and matched normal tissues, the latter being used as controls to distinguish somatic mutations from inherited variants. The teams analyzed the genes from 3,281 tumors, a collection of cancers of the breast, uterus, head and neck, colon and rectum, bladder, kidney, ovary, lung, brain and blood. In addition to finding common links among genes in different cancers, the scientists also identified a number of mutations exclusive to particular cancer types.

While the average number of mutated genes in tumors varied among the cancer types, most tumors had only two to six mutations in genes that drive cancer. This may be one reason why cancer is so common. Genes that have a significant effect on survival were also identified. These included tumor protein p53 (TP53), an already well-known cancer gene, occurred most commonly across the different tumor types. It was found in 42% of samples and routinely was associated with a poor prognosis, particularly in kidney cancer, head and neck cancer and acute myeloid leukemia. Another gene, Breast Cancer 1 (BRCA1) associated protein-1 (ubiquitin carboxy-terminal hydrolase) (BAP1), was also linked with an unfavorable prognosis, especially in patients with kidney and uterine cancer.

These discoveries set the stage for devising new diagnostic tools and more personalized cancer treatments. Li Ding, PhD, the senior author of the study, said, “Because we now know, for example, that genes mutated in leukemia also can be altered in breast cancer and that genetic errors in lung cancer also can show up in colon and rectal cancer, we think one inclusive diagnostic test that includes all cancer genes would be ideal. This would provide a more complete picture of what's going on in a tumor, and that information could be used to make decisions about treatment.” The study was published on October 16, 2013, in the journal Nature.

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Washington University School of Medicine



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Image: representation of a protein (blue), which contains three zinc fingers in complex with DNA (orange). The coordinating amino acid residues and zinc ions (green) are highlighted (Photo courtesy of Wikimedia Commons).

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