Wilkes, David C; Sailer, Verena; Xue, Hui; Cheng, Hongwei; Collins, Colin C; Gleave, Martin; Wang, Yuzhuo; Demichelis, Francesca; Beltran, Himisha; Rubin, Mark Andrew; Rickman, David S (2017). A germline FANCA alteration that is associated with increased sensitivity to DNA damaging agents. Cold Spring Harbor molecular case studies, 3(5) Cold Spring Harbor Laboratory Press 10.1101/mcs.a001487
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Defects in genes involved in DNA damage repair (DDR) pathway are emerging as novel biomarkers and targets for new prostate cancer drug therapies. A previous report revealed an association between an exceptional response to cisplatin treatment and a somatic loss of heterozygosity (LOH) of FANCA in a patient with metastatic prostate cancer who also harbored a germline FANCA variant (S1088F). Although germline FANCA mutations are the most frequent alterations in patients with Fanconi anemia, germline alterations are less common in prostate cancer. We hypothesized that the germline S1088F FANCA variant in combination with FANCA LOH was deleterious for FANCA function and contributed to the patient's exceptional response to cisplatin. We show that although it properly localizes to the nucleus, the S1088F FANCA mutant protein disrupts the FANC protein complex resulting in increased sensitivity to DNA damaging agents. Because molecular stratification is emerging as a strategy for treating men with metastatic, castrate-resistant prostate cancer harboring specific DDR gene defects, our findings suggest that more biomarker studies are needed to better define clinically relevant germline and somatic alterations.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie |
UniBE Contributor: |
Rubin, Mark Andrew |
Subjects: |
500 Science 500 Science > 570 Life sciences; biology |
ISSN: |
2373-2873 |
Publisher: |
Cold Spring Harbor Laboratory Press |
Language: |
English |
Submitter: |
Marla Rittiner |
Date Deposited: |
08 Mar 2018 13:02 |
Last Modified: |
05 Dec 2022 15:10 |
Publisher DOI: |
10.1101/mcs.a001487 |
PubMed ID: |
28864460 |
Uncontrolled Keywords: |
prostate cancer |
BORIS DOI: |
10.7892/boris.110751 |
URI: |
https://boris.unibe.ch/id/eprint/110751 |
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