Ovarian Cancer and the TCGA

Ovarian Cancer and the TCGA

George W. Sledge, MD, FASCO

Jul 04, 2011
The June 30th issue of Nature has a wonderful article from The Cancer Genome Atlas (TCGA) group entitled “Integrated Genomic Analyses of Ovarian Carcinoma.” It is a landmark publication, not just for ovarian cancer but for all of human cancer. The investigators, a stellar multi-institutional group “analysed messenger RNA expression, microRNAexpression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours.”

This is an astonishing amount of work in a huge number of ovarian cancers and is just the first of many such efforts that will be presented by the TCGA in the next few years. Similar efforts are underway in the International Cancer Genome Consortium (ICGC) and in other research consortia. In the next two or three years, cancer researchers will have an enormous volume of genomic data to play with. This data will all be online and available to all. We can confidently expect an explosion of analyses of this cancer and every other major cancer afflicting us. Much of the TCGA work is being funded with American Recovery & Reinvestment Act (ARRA) money, certainly among the best spent federal research dollars in recent decades.

So what have we learned about ovarian cancer? First, the incredible frequency of TP53 mutations, occurring in 96% of tumors. Secondly, ovarian cancer is a family of diseases: four transcriptional subtypes, three microRNA subtypes, and four promoter methylation subtypes. Thirdly, that there are many (too many?) druggable targets, based on the (many, low frequency) mutational events observed. Predominant among these, perhaps unsurprisingly, is PARP. I say unsurprisingly because this is the human cancer where PARP inhibitors appear to be having the greatest clinical impact based on initial trial data.

You can expect similar publications in several human cancers in the coming months and years. We are approaching the time where we will have a comprehensive understanding of the mutational landscape of human cancer: not just ovarian cancer, but all cancer. This will be followed, in the not too distant future (a decade, maybe less?), with regular deep sequencing of individual cancer and host genomes, with direct clinical application. I don’t think this is a utopian view of the future, merely a highly probable event given the rapidly evolving technology for genomic testing. What we will be able to accomplish once we have all of this data in hand remains to be seen, but the next few years will be exciting ones.

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