Molecular analysis of TCGA breast cancer histologic types
Aatish Thennavan,
Francisco Beca,
Youli Xia,
Susana Garcia-Recio,
Kimberly Allison,
Laura C. Collins,
Gary M. Tse,
Yunn-Yi Chen,
Stuart J. Schnitt,
Katherine A. Hoadley,
Andrew Beck,
Charles M. Perou
Affiliations
Aatish Thennavan
Oral and Craniofacial Biomedicine Program, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Francisco Beca
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
Youli Xia
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Susana Garcia-Recio
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Kimberly Allison
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
Laura C. Collins
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
Gary M. Tse
Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong
Yunn-Yi Chen
Department of Pathology and Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
Stuart J. Schnitt
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School and Breast Oncology Program, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA 02115, USA
Katherine A. Hoadley
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Andrew Beck
PathAI, Boston, MA, USA
Charles M. Perou
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Corresponding author
Summary: Breast cancer is classified into multiple distinct histologic types, and many of the rarer types have limited characterization. Here, we extend The Cancer Genome Atlas Breast Cancer (TCGA-BRCA) dataset with additional histologic type annotations in a total of 1,063 breast cancers. We analyze this extended dataset to define transcriptomic and genomic profiles of six rare, special histologic types: cribriform, micropapillary, mucinous, papillary, metaplastic, and invasive carcinoma with medullary pattern. We show the broader applicability of our constructed special histologic type gene signatures in the TCGA Pan-Cancer Atlas dataset with a predictive model that detects mucinous histologic type across cancers of other organ systems. Using a normal mammary cell differentiation score analysis, we order histologic types into a continuum from stem cell-like to luminal progenitor-like to mature luminal-like. Finally, we classify TCGA-BRCA into 12 consensus groups based on integrated genomic and histological features. We present a rich, openly accessible resource of genomic, molecular, and histologic characterization of TCGA-BRCA to enable studies across the range of breast cancers.
