Abstract 3407: Gene expression subtypes of high grade serous ovarian cancer in African American women
Authors: Doherty Jennifer A. , Greene Casey S. , Rudd James E. , Tafe Laura J. , Alberg Anthony J. , Bandera Elisa V. , Barnholtz-Sloan Jill , Bondy Melissa , Cote Michele L. , Funkhouser Ellen , Moorman Patricia G. , Peters Edward S. , Schwartz Ann G. , Terry Paul , Bentley Rex , Berchuck Andrew , Marks Jeffrey R. , Schildkraut Joellen M. 
Published: July 2016

Ovarian cancer accounts for 5% of cancer deaths and is the fifth leading cause of cancer death in women in the United States. While incidence is higher in European American (EA) than African American (AA) women, five-year survival is worse for AA women (36%) than EA women (44%). Access to appropriate surgery and treatment is a major contributor but does not completely explain this disparity. The Cancer Genome Atlas (TCGA) identified four gene expression-based subtypes of the most common and lethal histotype, high grade serous carcinoma (HGSC): mesenchymal, proliferative, differentiated, and immunoreactive. We sought to characterize similarities and differences in gene expression-based subtypes arising in AA and EA women to determine whether there are underlying biologic features that may influence survival. We performed two distinct analyses, first using TCGA data and second using cases from the population-based African American Cancer Epidemiology Study (AACES). For both we summarized differential expression patterns for each subtype with moderated t statistic vectors for &gt;10,000 genes using Significance Analysis of Microarrays. We calculated Pearson's correlations of these vectors to determine concordance of expression patterns between subtypes across EA and AA women. In TCGA, we observed correlations of subtype-specific expression patterns between the 24 AA and 475 EA tumors of 0.52-0.60 for each of the four subtypes. Thus, while analogous subtypes can be identified in AA and EA women, the magnitude of these correlations suggests that there are potential differences in gene expression patterns between AA and EA tumors that are assigned to the same subtype. We generated additional data from 58 AACES HGSC cases using the Affymetrix Human Transcriptome Array 2.0. Instead of assigning these tumors to previously-defined subtypes, we clustered samples to identify four subtypes de novo. We observed concordance with two of the TCGA subtypes; correlations for the mesenchymal-like and proliferative-like subtypes were 0.56-0.65. The mesenchymal-like subtype was more common in these AA women than in the TCGA EA women (33% versus 25%), and the proliferative-like subtype was marginally less common (14% versus 19%). Concordance for the differentiated-like subtype was considerably lower, at 0.21, and this subtype was less common in AA than EA women (19% versus 34%). Another subtype comprising 34% of the AA samples was only weakly correlated (-0.21-0.10) with any of the TCGA subtypes, suggesting that it is a novel subtype. The limited data available on HGSC in AA women suggest that at least two subtypes are comparable to those in EA women but differ in prevalence, and that there may be a novel subtype in AA women that does not strongly correspond to those described in EA women.

Citation Format: Jennifer A. Doherty, Casey S. Greene, James E. Rudd, Laura J. Tafe, Anthony J. Alberg, Elisa V. Bandera, Jill Barnholtz-Sloan, Melissa Bondy, Michele L. Cote, Ellen Funkhouser, Patricia G. Moorman, Edward S. Peters, Ann G. Schwartz, Paul Terry, Rex Bentley, Andrew Berchuck, Jeffrey R. Marks, Joellen M. Schildkraut. Gene expression subtypes of high grade serous ovarian cancer in African American women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3407.