FANCM

Overview

FANCM (FA Complementation Group M) encodes a DNA translocase component of the Fanconi anemia core complex, essential for interstrand crosslink repair. Splice-site and frameshift mutations in FANCM have been identified in gynaecologic carcinosarcoma, implicating homologous recombination repair deficiency in this tumor type.

Alterations observed in the corpus

  • Splice-site/frameshift mutations in 2/22 gynaecologic carcinosarcoma cases; identified by whole-exome sequencing PMID:25233892.
  • Fanconi-anaemia pathway lesion enriched in high-CNV PDAC clusters; nominates PARP inhibitor and cross-linking agent therapy PMID:25855536
  • FANCM is included in the FA pathway gene classifier used to identify carboplatin-responsive mCRPC; homozygous deleterious FANCM events associate with longer time on carboplatin (log-rank P = 0.02 for the full FA/ATM group) PMID:26928463
  • FANCM identified among recurrent germline pathogenic/likely pathogenic variants in an Indian familial young lung cancer cohort (Rastogi et al.), alongside ATM, CHEK2, BAP1, FANCA, FANCI, LZTR1, and XRCC3 PMID:27346245
  • One pLoF LP/PV identified by WES of 25 HBOC-related candidate genes in 372 pediatric cancer patients; burden OR=2.2, p=0.370 (non-significant single-cohort). PMID:29489754

Cancer types (linked)

  • UCS/MXOV (gynaecologic carcinosarcoma): 2/22 cases (9%) with FANCM defects; FANCM deficiency flags potential mitomycin sensitivity PMID:25233892.

Co-occurrence and mutual exclusivity

  • No co-occurrence or mutual exclusivity data reported in the corpus.

Therapeutic relevance

  • FANCM defects may confer sensitivity to mitomycin (DNA crosslinking agent) via impaired interstrand crosslink repair PMID:25233892.

Open questions

  • Whether FANCM-deficient carcinosarcomas respond to platinum agents or PARP inhibitors (analogous to BRCA1/2-deficient tumors) is untested in this cohort PMID:25233892.

Sources

This page was processed by entity-page-writer on 2026-05-15. - 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:29489754

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