FANCD2

Overview

FANCD2 is a central effector of the Fanconi anemia (FA) DNA repair pathway, activated by monoubiquitination in response to DNA interstrand crosslinks. Biallelic FANCD2 inactivation causes Fanconi anemia; somatic alterations occur in pancreatic and other solid tumors.

Alterations observed in the corpus

DNA double-strand-break and Fanconi-anaemia pathway lesion enriched in high-CNV PDAC clusters; nominates PARP inhibitor and cross-linking agent therapy PMID:25855536
Truncating mutation (1 tumor), homozygous deletion (2), and focal heterozygous loss in 6% of primary prostate cancers; contributes to the ~19% DNA-repair-deficient subset with potential PARP-inhibitor sensitivity PMID:26544944
FANCD2 expression is elevated in high-CCP mCRPC tumors; part of the 15-gene FA pathway signature correlated with E2F1 and RB1 loss; homozygous deleterious FANCD2 events qualify patients for the carboplatin-responsive DNA-repair-defect group (log-rank P = 0.02) PMID:26928463

Cancer types (linked)

PAAD: FA pathway lesions including FANCD2 are enriched in high-CNV PDAC clusters and nominate olaparib (PARP inhibitor) and mitomycin-C (cross-linking agent) as therapeutic candidates PMID:25855536

Co-occurrence and mutual exclusivity

Co-occurs with ATM, CHEK2, BRCA1, BRCA2, FANCF, FANCA, FANCM, and BCLAF1 as part of DNA damage response pathway lesions in PDAC PMID:25855536

Therapeutic relevance

Fanconi-anaemia pathway lesion; nominates PARP inhibitors (olaparib) and cross-linking agents (mitomycin-C) as therapeutic candidates in PDAC PMID:25855536

Open questions

Prevalence of biallelic vs. monoallelic FANCD2 inactivation in PDAC and whether monoallelic loss confers sufficient HRR deficiency for PARP inhibitor sensitivity.

Sources

PMID:25855536

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

This page was processed by wiki-cli on 2026-05-14. - PMID:26928463

This page was processed by wiki-cli on 2026-05-14.