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

doi:10.1016/j.xgen.2021.100067

Molecular analysis of TCGA breast cancer histologic types

Cell Genom. 2021 Dec 8;1(3):100067. doi: 10.1016/j.xgen.2021.100067.

Authors

Aatish Thennavan^{1

2}, Francisco Beca³, Youli Xia^{2

4}, Susana Garcia Recio^{2

4}, Kimberly Allison³, Laura C Collins⁵, Gary M Tse⁶, Yunn-Yi Chen⁷, Stuart J Schnitt⁸, Katherine A Hoadley^{2

4}, Andrew Beck⁹, Charles M Perou^{2

4

10}

Affiliations

¹ Oral and Craniofacial Biomedicine Program, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
³ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
⁵ Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
⁶ Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong.
⁷ Department of Pathology and Laboratory Medicine, University of California, San Francisco, CA, 94143, USA.
⁸ Department of Pathology, Brigham and Women's Hospital and Harvard Medical School; Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA 02115, USA.
⁹ PathAI, Boston, MA, USA.
¹⁰ Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Abstract

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 1063 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 histologic and genomic characterization of TCGA-BRCA to enable studies of the range of breast cancers.

Abstract

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