Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2014-08

AUTHORS

Weng Khong Lim, Choon Kiat Ong, Jing Tan, Aye Aye Thike, Cedric Chuan Young Ng, Vikneswari Rajasegaran, Swe Swe Myint, Sanjanaa Nagarajan, Nur Diyana Md Nasir, John R McPherson, Ioana Cutcutache, Gregory Poore, Su Ting Tay, Wei Siong Ooi, Veronique Kiak Mien Tan, Mikael Hartman, Kong Wee Ong, Benita K T Tan, Steven G Rozen, Puay Hoon Tan, Patrick Tan, Bin Tean Teh

ABSTRACT

Fibroadenomas are the most common breast tumors in women under 30 (refs. 1,2). Exome sequencing of eight fibroadenomas with matching whole-blood samples revealed recurrent somatic mutations solely in MED12, which encodes a Mediator complex subunit. Targeted sequencing of an additional 90 fibroadenomas confirmed highly frequent MED12 exon 2 mutations (58/98, 59%) that are probably somatic, with 71% of mutations occurring in codon 44. Using laser capture microdissection, we show that MED12 fibroadenoma mutations are present in stromal but not epithelial mammary cells. Expression profiling of MED12-mutated and wild-type fibroadenomas revealed that MED12 mutations are associated with dysregulated estrogen signaling and extracellular matrix organization. The fibroadenoma MED12 mutation spectrum is nearly identical to that of previously reported MED12 lesions in uterine leiomyoma but not those of other tumors. Benign tumors of the breast and uterus, both of which are key target tissues of estrogen, may thus share a common genetic basis underpinned by highly frequent and specific MED12 mutations. More... »

PAGES

877-880

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.3037

DOI

http://dx.doi.org/10.1038/ng.3037

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1020182683

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25038752


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