Molecular identification of basal-like breast cancer through genomic analyses across five cancer types.

Abstract

1011 Background: Common molecular alterations in different types of cancer are being identified and these might be successfully targeted regardless of the tumor´s tissue of origin. To better understand the genomic relationships among different types of cancer, we explored global gene expression patterns across breast, lung, ovarian, brain and colorectal cancers. Methods: A unified set of 1,707 samples of 5 human cancer types (breast [n=547], lung [squamous and adenocarcinomas, n=249], ovarian [serous carcinoma, n=489], brain [glioblastoma multiforme, n=202] and colorectal [n=220]) from The Cancer Genome Atlas (TCGA) project was evaluated. All microarrays were performed at the University of North Carolina under the same protocol and platform. All samples provided in each publication of TCGA were used, except for lung adenocarcinomas where we used TCGA public data. Consensus clustering was used to identify molecular entities, and breast cancer intrinsic subtyping was performed using the PAM50 predictor. Results: A total of 6 distinct and robust molecular entities were identified representing tumors from breast luminal/HER2-enriched, breast Basal-like, lung, ovarian, brain and colorectal cancers. Strikingly, 55%, 26%, 16% of Basal-like breast cancers were found to be more similar to squamous cell lung carcinomas, lung adenocarcinomas and ovarian cancers, respectively, compared to breast luminal/HER2-enriched tumors. Breast cancer intrinsic subtyping identified a Basal-like profile in 55% of squamous cell lung cancers, 53% of ovarian cancers and 8% of lung adenocarcinomas. Finally, single genes and gene signatures tracking cancer-related biological processes such as proliferation, angiogenesis and immune activation were found highly expressed in different proportions across the 6 molecular entities. Conclusions: These data suggest that breast tumors of the Basal-like subtype have a distinct cell of origin compared to luminal/HER2-enriched tumors. Clinical trials focusing on tumors with common profiles and/or biomarker expression rather than their tissue of origin are warranted with a special focus on Basal-like breast cancer, squamous cell lung carcinoma and serous ovarian cancer.