FANCL
Overview
FANCL (Fanconi Anemia Complementation Group L) is the catalytic E3 ubiquitin ligase subunit of the FA core complex, directly responsible for monoubiquitination of FANCD2 and FANCI at sites of interstrand DNA crosslink damage. Loss of FANCL abrogates the entire FA pathway, causing severe HR deficiency. In cancer, somatic FANCL inactivation is part of the FA-deficiency signature associated with sensitivity to platinum-based chemotherapy.
Alterations observed in the corpus
- FANCL is part of the FA pathway gene classifier used in mCRPC; homozygous deleterious FANCL 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 — FANCL 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
- FANCL 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 FANCL 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 FANCL as a standalone biomarker is needed. PMID:26928463
Sources
This page was processed by crosslinker on 2026-05-14.