FANCA

Overview

FANCA (Fanconi Anemia Complementation Group A) encodes a core component of the Fanconi anemia (FA) DNA damage-repair complex. The FA pathway is activated by DNA interstrand crosslinks and replication-fork stalling, coordinating monoubiquitination of FANCD2/FANCI and downstream homologous-recombination (HR) repair. Germline biallelic loss of FANCA causes Fanconi anemia syndrome; in cancer, somatic FANCA alterations contribute to HR deficiency (HRD), genome instability, and clonal evolution — particularly in tumors under cytotoxic therapeutic pressure.

Alterations observed in the corpus

  • FANCA was identified as part of a cluster of DNA repair gene alterations (alongside RAD51B, RAD21, RAD51C, ATR, ATM, and FANCC) detected exclusively at relapse in fusion-negative rhabdomyosarcoma (FN-RMS) patients with higher overall mutational counts, suggesting these alterations arise under selective pressure during disease progression. PMID:37730754
  • FANCA identified as a DNA damage repair gene with non-silent variants in metastatic UC (UC-GENOME cohort) PMID:36333289
  • Listed as a gene observed in the TCGA papillary thyroid carcinoma (PTC) cohort (thca_tcga_pub); specific alteration details not described in the narrative sections of this paper. PMID:25417114
  • 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
  • Broader DNA-repair pathway alteration contributing to 22.7% aggregate HRR deficiency in mCRPC PMID:26000489
  • FANCA is part of the 15-gene FA pathway signature upregulated in high-CCP mCRPC tumors; homozygous deleterious FANCA events classify patients into the DNA-repair-defect group with significantly longer carboplatin response (log-rank P = 0.02; 20 treated men) PMID:26928463
  • FANCA identified among recurrent germline pathogenic/likely pathogenic variants in an Indian familial young lung cancer cohort (Rastogi et al.), alongside ATM, CHEK2, BAP1, FANCI, FANCM, LZTR1, and XRCC3 PMID:27346245
  • FANCA germline heterozygous deletion combined with somatic stopgain mutation identified in one HNSC patient sequenced with MSK-IMPACT; proposed as a potential cisplatin-sensitivity biomarker PMID:27442865
  • Identified as a somatic HR pathway gene in prostate cancer; CDK12 and FANCA loss hypothesized to confer PARP inhibitor sensitivity, though clinical significance remains emerging per OncoKB at time of publication PMID:28825054

Cancer types (linked)

  • RMS / ERMS (fusion-negative): FANCA alterations were observed only at relapse, clustered with other DNA repair gene defects in FN-RMS cases harboring elevated mutation burdens. The pattern is consistent with progressive genomic instability rather than a founding driver event. PMID:37730754

Co-occurrence and mutual exclusivity

  • FANCA alterations co-occurred with other FA/HR pathway genes (FANCC, RAD51B, RAD51C) and double-strand-break response genes (ATR, ATM, RAD21) in the same FN-RMS relapse samples, indicating a broad DNA repair deficiency phenotype at relapse. PMID:37730754

Therapeutic relevance

  • HR-deficient tumors with FA pathway loss may be sensitized to PARP inhibitors or platinum-based crosslinking agents; no direct therapeutic data for FANCA in RMS are available in the current corpus.

Open questions

  • Whether FANCA alterations in relapsed FN-RMS are clonally selected by prior alkylating-agent chemotherapy or arise stochastically remains unresolved. PMID:37730754
  • Functional validation (e.g., FANCD2 monoubiquitination assay, RAD51 foci) has not been reported for these relapse-acquired somatic FANCA variants in the corpus.

Sources

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

This page was processed by entity-page-writer on 2026-05-15. - PMID:27346245

This page was processed by entity-page-writer on 2026-05-15. - PMID:27442865

This page was processed by entity-page-writer on 2026-05-15. - PMID:28825054

This page was processed by wiki-cli on 2026-05-15.