FANCI

Overview

FANCI (Fanconi Anemia Complementation Group I) forms a heterodimer with FANCD2 that, upon monoubiquitination by the FA core complex, localizes to sites of DNA damage to coordinate interstrand crosslink repair. FANCI expression is elevated in highly proliferative tumors, particularly downstream of RB1 loss and E2F1 activation. In mCRPC, elevated FANCI expression is part of the FA pathway signature that co-segregates with cell-cycle progression.

Alterations observed in the corpus

  • FANCI expression is elevated in high-CCP mCRPC tumors as part of the FA complex gene set (alongside FANCA, FANCD2, BRCA1, BRCA2); correlated with E2F1 and RB1 loss; part of the 15-gene FA signature (r = 0.78 with CCP score, P < 0.001); homozygous deleterious FANCI events qualify patients for the DNA-repair-defect carboplatin-response group (log-rank P = 0.02). PMID:26928463
  • FANCI identified among recurrent germline pathogenic/likely pathogenic variants in an Indian familial young lung cancer cohort (Rastogi et al.), alongside ATM, CHEK2, BAP1, FANCA, FANCM, LZTR1, and XRCC3 PMID:27346245
  • FANCI is overexpressed in the poor-prognosis STLMS iCluster C1, grouped with CCNE2 and MCM2 as cell-cycle / DNA replication / DNA-repair genes characterizing the worse-prognosis LMS subtype PMID:29100075

Cancer types (linked)

  • PRAD — FANCI expression is a marker of the FA/proliferative phenotype in mCRPC driven by RB1 loss; somatic FANCI loss is part of the DNA-repair-defect classifier associated with longer carboplatin response. PMID:26928463

Co-occurrence and mutual exclusivity

  • FANCI alterations and overexpression co-occur with RB1 loss, elevated E2F1, and high CCP score in mCRPC; the FANCD2-FANCI heterodimer is a functional unit within the FA repair pathway. PMID:26928463

Therapeutic relevance

  • Homozygous deleterious FANCI 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 FANCI as a standalone biomarker is needed. PMID:26928463

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:27346245

This page was processed by entity-page-writer on 2026-05-15. - PMID:29100075

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