Defective Genome Instability Suppressing Genes May Cause Some Types of Cancer

Cancer researchers reported in a recent study that defects in the expression of genes that suppress gross chromosomal rearrangements (GCRs) were linked to more than 93% of the ovarian and 66% of the colorectal cancer cases they had examined.

Investigators at the University of California, San Diego (USA) worked with the yeast Saccharomyces cerevisiae to identify genome instability suppressing (GIS) genes that acted to prevent chromosomal rearrangements. They reported in the April 13, 2016, online edition of the journal Nature Communications that by using this platform they had been able to identify182 GIS genes that suppressed GCR formation. Another 438 cooperatively acting GIS genes (cGIS) were identified that were not GIS genes, but suppressed the increased genome instability caused by individual query mutations.

Analysis of data derived from The Cancer Genome Atlas (TCGA) allowed the investigators to predict which human genes were associated with GIS pathways. This analysis revealed that a minimum of 93% of ovarian and 66% of colorectal cancer cases had defects affecting one or more predicted GIS gene. These defects included loss-of-function mutations, copy-number changes associated with reduced expression, and silencing. In contrast, acute myeloid leukemia cases did not appear to have defects affecting the predicted GIS genes.

"Mutated GIS genes have long been suspected of playing a role in the development of many types of cancers, but identifying them has been difficult due in large part to a lack of comprehensive GCR tests, or assays, in mammalian systems," said first author Dr. Christopher Putnam, adjunct assistant professor of medicine at the University of California, San Diego School of Medicine. "Before our experiment, only a few dozen cGIS genes were known. Now we know of hundreds. Understanding this process allows us to think more about how carcinogenesis proceeds and it might give us insights into defects that could be therapeutically actionable in the future."

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