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Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.

Publication ,  Journal Article
Lim, WK; Ong, CK; Tan, J; Thike, AA; Ng, CCY; Rajasegaran, V; Myint, SS; Nagarajan, S; Nasir, NDM; McPherson, JR; Cutcutache, I; Poore, G ...
Published in: Nat Genet
August 2014

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.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

August 2014

Volume

46

Issue

8

Start / End Page

877 / 880

Location

United States

Related Subject Headings

  • Young Adult
  • Transcriptome
  • Sequence Analysis, DNA
  • Neoplasm Recurrence, Local
  • Mutation
  • Middle Aged
  • Mediator Complex
  • Humans
  • Fibroadenoma
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Lim, W. K., Ong, C. K., Tan, J., Thike, A. A., Ng, C. C. Y., Rajasegaran, V., … Teh, B. T. (2014). Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nat Genet, 46(8), 877–880. https://doi.org/10.1038/ng.3037
Lim, Weng Khong, Choon Kiat Ong, Jing Tan, Aye Aye Thike, Cedric Chuan Young Ng, Vikneswari Rajasegaran, Swe Swe Myint, et al. “Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.Nat Genet 46, no. 8 (August 2014): 877–80. https://doi.org/10.1038/ng.3037.
Lim WK, Ong CK, Tan J, Thike AA, Ng CCY, Rajasegaran V, et al. Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nat Genet. 2014 Aug;46(8):877–80.
Lim, Weng Khong, et al. “Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.Nat Genet, vol. 46, no. 8, Aug. 2014, pp. 877–80. Pubmed, doi:10.1038/ng.3037.
Lim WK, Ong CK, Tan J, Thike AA, Ng CCY, Rajasegaran V, Myint SS, Nagarajan S, Nasir NDM, McPherson JR, Cutcutache I, Poore G, Tay ST, Ooi WS, Tan VKM, Hartman M, Ong KW, Tan BKT, Rozen SG, Tan PH, Tan P, Teh BT. Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nat Genet. 2014 Aug;46(8):877–880.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

August 2014

Volume

46

Issue

8

Start / End Page

877 / 880

Location

United States

Related Subject Headings

  • Young Adult
  • Transcriptome
  • Sequence Analysis, DNA
  • Neoplasm Recurrence, Local
  • Mutation
  • Middle Aged
  • Mediator Complex
  • Humans
  • Fibroadenoma
  • Female