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Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type.

Publication ,  Journal Article
Witkowski, L; Carrot-Zhang, J; Albrecht, S; Fahiminiya, S; Hamel, N; Tomiak, E; Grynspan, D; Saloustros, E; Nadaf, J; Rivera, B; Gilpin, C ...
Published in: Nat Genet
May 2014

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is the most common undifferentiated ovarian malignancy in women under 40 years of age. We sequenced the exomes of six individuals from three families with SCCOHT. After discovering segregating deleterious germline mutations in SMARCA4 in all three families, we tested DNA from a fourth affected family, which also carried a segregating SMARCA4 germline mutation. All the familial tumors sequenced harbored either a somatic mutation or loss of the wild-type allele. Immunohistochemical analysis of these cases and additional familial and non-familial cases showed loss of SMARCA4 (BRG1) protein in 38 of 40 tumors overall. Sequencing of cases with available DNA identified at least one germline or somatic deleterious SMARCA4 mutation in 30 of 32 cases. Additionally, the SCCOHT cell line BIN-67 had biallelic deleterious mutations in SMARCA4. Our findings identify alterations in SMARCA4 as the major cause of SCCOHT, which could lead to improvements in genetic counseling and new treatment approaches.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

May 2014

Volume

46

Issue

5

Start / End Page

438 / 443

Location

United States

Related Subject Headings

  • Transcription Factors
  • Sequence Analysis, DNA
  • Ovarian Neoplasms
  • Nuclear Proteins
  • Mutation
  • Molecular Sequence Data
  • In Situ Hybridization, Fluorescence
  • Immunohistochemistry
  • Immunoblotting
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Witkowski, L., Carrot-Zhang, J., Albrecht, S., Fahiminiya, S., Hamel, N., Tomiak, E., … Foulkes, W. D. (2014). Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type. Nat Genet, 46(5), 438–443. https://doi.org/10.1038/ng.2931
Witkowski, Leora, Jian Carrot-Zhang, Steffen Albrecht, Somayyeh Fahiminiya, Nancy Hamel, Eva Tomiak, David Grynspan, et al. “Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type.Nat Genet 46, no. 5 (May 2014): 438–43. https://doi.org/10.1038/ng.2931.
Witkowski L, Carrot-Zhang J, Albrecht S, Fahiminiya S, Hamel N, Tomiak E, et al. Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type. Nat Genet. 2014 May;46(5):438–43.
Witkowski, Leora, et al. “Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type.Nat Genet, vol. 46, no. 5, May 2014, pp. 438–43. Pubmed, doi:10.1038/ng.2931.
Witkowski L, Carrot-Zhang J, Albrecht S, Fahiminiya S, Hamel N, Tomiak E, Grynspan D, Saloustros E, Nadaf J, Rivera B, Gilpin C, Castellsagué E, Silva-Smith R, Plourde F, Wu M, Saskin A, Arseneault M, Karabakhtsian RG, Reilly EA, Ueland FR, Margiolaki A, Pavlakis K, Castellino SM, Lamovec J, Mackay HJ, Roth LM, Ulbright TM, Bender TA, Georgoulias V, Longy M, Berchuck A, Tischkowitz M, Nagel I, Siebert R, Stewart CJR, Arseneau J, McCluggage WG, Clarke BA, Riazalhosseini Y, Hasselblatt M, Majewski J, Foulkes WD. Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type. Nat Genet. 2014 May;46(5):438–443.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

May 2014

Volume

46

Issue

5

Start / End Page

438 / 443

Location

United States

Related Subject Headings

  • Transcription Factors
  • Sequence Analysis, DNA
  • Ovarian Neoplasms
  • Nuclear Proteins
  • Mutation
  • Molecular Sequence Data
  • In Situ Hybridization, Fluorescence
  • Immunohistochemistry
  • Immunoblotting
  • Humans