The RAD51D c.82G>A (p.Val28Met) variant disrupts normal splicing and is associated with hereditary ovarian cancer Journal Article

   


Authors: Yang, C.; Arnold, A. G.; Catchings, A.; Rai, V.; Stadler, Z. K.; Zhang, L.
Article Title: The RAD51D c.82G>A (p.Val28Met) variant disrupts normal splicing and is associated with hereditary ovarian cancer
Abstract: Purpose: Mutations in RAD51D are associated with a predisposition to primary ovarian, fallopian tube, and peritoneal carcinoma. Our study aims to characterize a RAD51D missense variant in a hereditary ovarian cancer family. Methods: The effects of the RAD51D c.82G>A (p.Val28Met) variant on mRNA splicing were evaluated and characterized using RT-PCR, cloning and DNA sequencing. Results: This variant completely disrupts normal splicing and results in the loss of 3′end of 5′UTR and the entire exon 1 (c.-86_c.82), which presumably leads to loss of the RAD51D protein. The RAD51D c.82G>A (p.Val28Met) variant is clinically significant and classified as likely pathogenic. Conclusions: Our results indicate that the RAD51D c.82G>A (p.Val28Met) variant contributes to cancer predisposition through disruption of normal mRNA splicing. The identification of this variant in an individual affected with high-grade serous fallopian tube cancer suggests that the RAD51D variant may contribute to predisposition to the ovarian cancer in this family. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
Keywords: adult; clinical article; middle aged; exon; genetic analysis; ovarian cancer; cancer susceptibility; ovary cancer; protein depletion; genetic variability; molecular cloning; oncogene; messenger rna; 5' untranslated region; real time polymerase chain reaction; 3' untranslated region; rna splicing; splicing; dna sequencing; human; female; priority journal; article; hereditary tumor syndrome; rad51d gene; missense variant; rad51d
Journal Title: Breast Cancer Research and Treatment
Volume: 185
Issue: 3
ISSN: 0167-6806
Publisher: Springer  
Date Published: 2021-02-01
Start Page: 869
End Page: 877
Language: English
DOI: 10.1007/s10549-020-06066-7
PUBMED: 33452952
PROVIDER: scopus
PMCID: PMC8414856
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85100216541&doi=10.1007%2fs10549-020-06066-7&partnerID=40&md5=d92fa57e0e2d5935b2c640066cbc71f7
Notes: Article -- Export Date: 1 April 2021 -- Source: Scopus
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MSK Authors
  1. Liying Zhang
    129 Zhang
  2. Zsofia Kinga Stadler
    391 Stadler
  3. Angela Arnold
    42 Arnold
  4. Ciyu Yang
    26 Yang
  5. Amanda Catchings
    20 Catchings
  6. Vikas Kumar Rai
    9 Rai
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