FANCG
Overview
FANCG (Fanconi Anemia Complementation Group G, also known as XRCC9) is a subunit of the FA core complex essential for FANCD2 monoubiquitination and interstrand crosslink repair. Biallelic germline FANCG mutations cause Fanconi anemia. In cancer, somatic FANCG inactivation results in homologous recombination deficiency and increased sensitivity to DNA-crosslinking agents.
Alterations observed in the corpus
- FANCG is part of the FA pathway gene classifier used in mCRPC; homozygous deleterious FANCG 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 reduced proliferation in prostate cancer cell lines and increased gamma-H2AX after carboplatin exposure. PMID:26928463
Cancer types (linked)
- PRAD — FANCG 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
- FANCG alterations co-occur with other FA pathway gene losses and with elevated E2F1 expression downstream of RB1 loss in high-CCP mCRPC tumors. PMID:26928463
Therapeutic relevance
- Homozygous deleterious FANCG events support classification of mCRPC patients as DNA-repair deficient; such patients had significantly longer responses to carboplatin (log-rank P = 0.02). PMID:26928463
Open questions
- The carboplatin response analysis is based on 20 treated men using time-on-drug as surrogate; prospective validation of FANCG as a standalone biomarker is needed. PMID:26928463
Sources
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