A huge cancer genome project has highlighted how DNA that doesn’t code for proteins is still important for keeping our cells on track.
The Pan-Cancer Analysis of Whole Genomes analyzed more than 2,600 tumors from 38 tissues, looking for causative mutations and patterns. Previous work had concentrated on the regions of the genome that code for proteins, but a significant proportion of cancer patients’ tumors don’t carry known “driver” (causative) mutations in protein-coding regions. So this project went out into what used to be called “junk DNA” or the “dark matter” of the genome.
Emory bioinformatics postdoc Matthew Reyna is the first author of one of 23 papers on the PCAWG project, published Feb. 5 in the Nature family of journals. His paper in Nature Communications looks at mutations in non-coding regions of the genome in tumors, analyzing which biological processes are affected.
Some of these were mutations in the promoters of genes encoding well-known cancer suppressors such as p53, but the project also identified new genes containing cancer-driving mutations. A promoter is the stretch of DNA that tells the cell “make RNA copies starting here”.
Reyna contributed to the project while he was at Princeton, working with Benjamin Raphael, and at Emory as well. More recently, he’s been investigating protein-protein interactions with Haian Fu, Andrey Ivanov and others as part of the Cancer Target Discovery and Development (CTD2) project.
In honor of Fathersâ€™ Day, we are examining a connection between two older-male-centric topics: statins and prostate cancer.
Statins are a very widely prescribed class of drugs used to lower cholesterol levels, for the purpose of preventing cardiovascular disease. In cell culture, they appear to kill prostate cancer cells, but the epidemiological evidence is murkier. Statin effects on prostate cancer incidence have beenÂ up in the air, but recent reports point to the possibility that starting statins may slow progression, after a man has been diagnosed with prostate cancer.
Winship Cancer Institute researchers have some new results that shed some light on this effect. John Petros, Rebecca Arnold and Qian Sun have found that mutations in mitochondrial DNA make prostate cancer cells resistant to cell death induced by simvastatin [Zocor, the most potent generic statin]. Sun recently presented the results at the American Urological Association meeting in Orlando.
In other forms of cancer such as breast and lung cancer, genomic profiling can determine what DNA mutations are driving cancer growth and what drugs are likely to be effective in fighting the cancer. The prostate cancer field has not reached the same point, partly because prostate cancers areÂ not generallyÂ treated with chemotherapy until late in the game, Petros says. But potentially, information on mitochondrial mutations could guide decisions on whether to initiate statin (or another) therapy.
â€œThis is part of our soapbox,â€ heÂ says. â€œWhen we are looking at mutational effects on prostate cancer, letâ€™s be sure to include the mitochondrial genome.â€
Winship’s Carlos Moreno and his colleagues areÂ working on the related question of biomarkers that predict prostate cancer progression, after prostatectomy surgery and potentially after just a biopsy.