FHIT

Overview

FHIT (Fragile Histidine Triad, 3p14.2) encodes a diadenosine triphosphate hydrolase and is located within the FRA3B common fragile site, one of the most frequently disrupted genomic regions in human cancer. FHIT loss is observed across a wide range of solid tumors. In melanoma, FHIT is among the most recurrently rearranged genes, consistent with its fragile site location and susceptibility to structural genomic instability.

Alterations observed in the corpus

  • Recurrent structural rearrangements in 6/25 melanomas in a WGS discovery cohort (25 tumors, Broad/Sanger); one of the most frequently rearranged genes alongside PTEN, MAGI2, MACROD2, CSMD1, and RBFOX1 PMID:22622578
  • Focal deletion on 3p in OSCC; candidate tumor suppressor in HNSCC PMID:23619168
  • FHIT (fragile histidine triad) shows germline and somatic variants observed uniquely in familial intestinal gastric cancer (FIGC) vs. sporadic intestinal GC, suggesting a role in familial gastric cancer predisposition. PMID:24816255
  • Recurrent focal deletion on 3p in SCLC (110-tumour WGS cohort) PMID:26168399
  • Fragile-site deletions at FHIT (3p) higher in esophageal adenocarcinoma (EAC) vs CIN gastric cancer in the TCGA esophageal carcinoma multi-platform study; FHIT low expression part of the poor-prognosis transcriptomic signature in one Ewing sarcoma patient PMID:28052061.

Cancer types (linked)

  • MEL (melanoma): FHIT rearrangements observed in 6/25 discovery tumors in a WGS study; alterations consistent with fragile site vulnerability under replicative stress PMID:22622578

Co-occurrence and mutual exclusivity

  • Rearrangements co-occur with high structural rearrangement burden in melanoma; no specific co-mutation pattern reported PMID:22622578

Therapeutic relevance

  • No direct therapeutic implications reported in this corpus; FHIT loss is generally considered a passenger event at fragile sites.

Open questions

  • Whether FHIT rearrangements in melanoma are driver events or fragile site-associated passenger lesions remains unclear PMID:22622578

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:23619168

This page was processed by crosslinker on 2026-05-14. - PMID:24816255

This page was processed by crosslinker on 2026-05-14. - PMID:26168399

This page was processed by crosslinker on 2026-05-14. - PMID:28052061

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