NCI Cancer Bulletin for February 22, 2011 - National Cancer Institute: More DNA Rearrangements Found in Prostate Cancers

More DNA Rearrangements Found in Prostate Cancers

The first study to compare the genomic sequences of multiple prostate tumors has found recurring rearrangements of DNA that may contribute to the development of the disease. Using tumor samples from seven patients, the researchers confirmed the existence of previously identified genetic changes associated with prostate cancer and discovered other alterations that could lead to new treatments for the disease.

Drs. Levi Garraway of the Dana-Farber Cancer Institute and Mark Rubin of Weill Cornell Medical College and their colleagues reported the findings February 10 in Nature. The study was funded in part by NCI’s Early Detection Research Network.

Previous studies have shown that many prostate tumors have fused genes, changes that occur when DNA sequences from different parts of the genome are linked together inappropriately. In the current study, three of the seven patients had the fusion gene TMPRSS2-ERG, which occurs in approximately half of all prostate cancers, and according to a 2008 study, may contribute to the disease.

In addition, the researchers detected approximately 90 genomic rearrangements per tumor, although these were not all associated with prostate cancer. (A genomic study of breast tumors reported a similar prevalence of rearrangements, but the mechanisms by which they occur may differ in the two cancers, the researchers noted.)

An analysis of the chromosomal rearrangements “revealed a distinctive pattern of balanced breaking and rejoining not previously observed in solid tumors,” the study authors wrote. Some of the rearrangements appeared to disrupt multiple genes in parallel, and these changes could affect the regulation of genes associated with cancer, the authors suggested.

“This study underscores the importance of doing systematic whole-genome sequencing in cancer,” said the study’s first author, Dr. Michael Berger, who conducted the research while at the Broad Institute. “Some of these rearrangements would not have been detected by targeted sequencing approaches that focus on just part of the genome rather than the whole.”

NCI Cancer Bulletin for February 22, 2011 - National Cancer Institute