Genomic landscapes of breast fibroepithelial tumors View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2015-11

AUTHORS

Jing Tan, Choon Kiat Ong, Weng Khong Lim, Cedric Chuan Young Ng, Aye Aye Thike, Ley Moy Ng, Vikneswari Rajasegaran, Swe Swe Myint, Sanjanaa Nagarajan, Saranya Thangaraju, Sucharita Dey, Nur Diyana Md Nasir, Giovani Claresta Wijaya, Jing Quan Lim, Dachuan Huang, Zhimei Li, Bernice Huimin Wong, Jason Yong Sheng Chan, John R McPherson, Ioana Cutcutache, Gregory Poore, Su Ting Tay, Wai Jin Tan, Thomas Choudary Putti, Buhari Shaik Ahmad, Philip Iau, Ching Wan Chan, Anthony P H Tang, Wei Sean Yong, Preetha Madhukumar, Gay Hui Ho, Veronique Kiak Mien Tan, Chow Yin Wong, Mikael Hartman, Kong Wee Ong, Benita K T Tan, Steven G Rozen, Patrick Tan, Puay Hoon Tan, Bin Tean Teh

ABSTRACT

Breast fibroepithelial tumors comprise a heterogeneous spectrum of pathological entities, from benign fibroadenomas to malignant phyllodes tumors. Although MED12 mutations have been frequently found in fibroadenomas and phyllodes tumors, the landscapes of genetic alterations across the fibroepithelial tumor spectrum remain unclear. Here, by performing exome sequencing of 22 phyllodes tumors followed by targeted sequencing of 100 breast fibroepithelial tumors, we observed three distinct somatic mutation patterns. First, we frequently observed MED12 and RARA mutations in both fibroadenomas and phyllodes tumors, emphasizing the importance of these mutations in fibroepithelial tumorigenesis. Second, phyllodes tumors exhibited mutations in FLNA, SETD2 and KMT2D, suggesting a role in driving phyllodes tumor development. Third, borderline and malignant phyllodes tumors harbored additional mutations in cancer-associated genes. RARA mutations exhibited clustering in the portion of the gene encoding the ligand-binding domain, functionally suppressed RARA-mediated transcriptional activation and enhanced RARA interactions with transcriptional co-repressors. This study provides insights into the molecular pathogenesis of breast fibroepithelial tumors, with potential clinical implications. More... »

PAGES

1341-1345

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.3409

DOI

http://dx.doi.org/10.1038/ng.3409

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1003387908

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26437033


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