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Gene project identifying unknown targets for serous ovarian carcinoma
Preliminary results from The Cancer Genome Atlas Project on Serous Ovarian Cancer reveal the complexity of the disease.
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SGO 40th Annual Meeting on Women’s Cancer
The Cancer Genome Atlas Project researchers, working to identify clinically relevant targets for the treatment of serous ovarian carcinoma, have identified novel regions of loss and gain and novel mutations requiring further analysis, according to preliminary data presented at the Society of Gynecologic Oncologists’ 40th Annual Meeting on Women’s Cancer.
The aim of the three-year pilot project is to catalog genetic changes among three diseases: glioblastoma multiforme, serous ovarian carcinoma and squamous carcinoma of the lung. To date, researchers have processed 264 serous ovarian carcinoma bio-specimens. The target accrual is 500 high-grade serous ovarian carcinoma samples.
According to Douglas A. Levine, MD, of the Memorial Sloan-Kettering Cancer Center in New York, who presented the results, copy number data showed extensive regions of gain and loss across the entire genome including large deletions on chromosomes 4, 13, 16, and 17. RB1, PTEN and CCNE1 were among those known genes re-identified with recurrent amplifications or deletions. Additionally, new regions of loss and gain were identified, though additional samples are required for confirmation.
Mutations in known oncogenes and tumor suppressor genes such as MYC, TP53 and BRCA1 have also been identified with preliminary sequence analysis. Levine noted the complexity of serous ovarian cancer, suggesting it is not just one disease, but rather many diseases that look alike under the microscope.
“TCGA intends to write a new book on genomes and genetics,” Levine said. “Though some of the discovery will not be novel, the high-quality tissue specimens and breadth of progress will allow for the identification of previously unknown findings.” – by Stacey L. Adams
Right now, we only know about the genes that cause 10% of ovarian cancers and these are primarily related to BRCA mutations. The interesting thing about this presentation is that they found another mutation that was very common and that they feel is a causative factor for hereditary ovarian cancer. These results are preliminary and of course will need to be confirmed in another series of patient tissues. This was a tissue genomic analysis, but the concept that we might be able to identify another causative gene to identify people who are at risk to develop ovarian cancer pretty early is very exciting. Up to this point, we've been dealing with the BRCA gene which has allowed us to identify people who are at risk for about 10% of ovarian cancers. That's great, but we're still missing the other 90%.
This presentation was exciting because it may identify another group of patients who are genetically at risk, which prior to this point we have not been able to identify. The beauty of that is that we might be able to intervene and consider genetic testing and prophylactic surgery once people are done with child bearing to avoid ovarian cancer development.
Our main problem with ovarian cancer is that most patients present with very advanced stage disease, not because of anything that they've done wrong, but because we have no way of diagnosing the disease at an early stage. Even in very good screening programs where people are being followed on an every four- to six-month basis with ultrasound, the cancers that were diagnosed in our last national ovarian cancer screening system were all advanced stage disease. So we haven't really made any impact on diagnosing early stage disease; which is why we're so excited about the chance to identify people who are at very high risk and consider prophylactic oophorectomy.
– Peter G. Rose, MD
Section Head and Fellowship Director of Gynecologic Oncology,
Department of Obstetrics and Gynecology, Cleveland Clinic
For more information:
- Levine DA. #LBA1. Presented at: Society of Gynecologic Oncologists’ 40th Annual Meeting on Women’s Cancer; Feb. 5-8, 2009; San Antonio.