FANCB
Overview
FANCB (Fanconi Anemia Complementation Group B) encodes a subunit of the FA core complex required for monoubiquitination of the FANCD2-FANCI heterodimer in response to DNA interstrand crosslinks. Germline FANCB mutations cause the most severe subtype of Fanconi anemia syndrome. In cancer, somatic FANCB loss contributes to homologous recombination deficiency and may sensitize tumors to DNA-crosslinking agents such as platinum compounds.
Alterations observed in the corpus
- FANCB is part of the FA pathway gene classifier used in mCRPC; homozygous deleterious FANCB events qualify patients for the DNA-repair-defect group that showed significantly longer time on carboplatin chemotherapy (log-rank P = 0.02; n=20 treated men at rapid autopsy); siRNA knockdown of individual FA genes (including FANCB) reduced proliferation in prostate cancer cell lines and increased gamma-H2AX after carboplatin exposure. PMID:26928463
Cancer types (linked)
- PRAD — FANCB is part of the FA gene set whose homozygous loss classifies mCRPC patients as DNA-repair deficient; these patients had significantly longer carboplatin response in a rapid-autopsy cohort of 63 men. PMID:26928463
Co-occurrence and mutual exclusivity
Therapeutic relevance
- Homozygous deleterious FANCB events support classification of mCRPC patients as DNA-repair deficient; such patients had significantly longer responses to carboplatin in a cohort of 20 treated men (log-rank P = 0.02). PMID:26928463
Open questions
- The carboplatin response analysis is based on 20 treated men using time-on-drug as a surrogate; prospective validation of FANCB as a standalone biomarker is needed. PMID:26928463
Sources
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