Summary There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, FLI1) or mutations (SPOP, FOXA1, IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1-mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.

We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development.

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While advances in science and technology have increased options for treating breast cancer, current social trends have changed the way people deal with this disease. Women in the United States are no longer simply passive patients, but rather they are survivors, advocates and activists who are speaking up for themselves and speaking out for issues relevant to the treatment and prevention of breast cancer. As the discoveries of basic science have been translated to better clinical treatment, a new sense of hope has emerged. Quality of life now shares the spotlight with quantity of life as breast cancer has shifted from an acute to a chronic condition and as the numbers of long-term survivors increase. While this new population tends to have more optimistic expectations for survival, they are also expressing concerns about issues affecting their lives through and beyond treatment. These issues include, but are not limited to, such concerns as efficient and accurate diagnosis, the complexity of treatment decisions, access to quality cancer care, informed consent, privacy issues, availability of supportive care treatments, and effective communication skills, especially with their physicians. Survivors are also concerned about the impact of their disease on spouses and family, on fertility and sexuality issues, on their employment and (in the USA) insurability, and on their long-term survival. The identification of these increasing issues has given rise to a consumer movement that encourages a shift away from powerless victim to empowered survivor.

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