RECQL4

Overview

RECQL4 encodes a RecQ-family DNA helicase involved in DNA replication initiation, repair of double-strand breaks, and maintenance of genome stability. Germline RECQL4 mutations cause Rothmund-Thomson syndrome and are associated with osteosarcoma predisposition. RECQL4 germline variants have been identified in anaplastic thyroid carcinoma (ATC), suggesting a role in cancer predisposition for this aggressive histology.

Alterations observed in the corpus

  • RECQL4 germline variants detected in 5% of anaplastic thyroid carcinoma (ATC) patients in the Global Anaplastic Thyroid Cancer Initiative (GATCI) cohort (n=213 ATC regions from 292 patients); identified as the most frequently observed germline cancer predisposition gene variant in this cohort PMID:38412093.
  • Added to significant gene list by inactivation-bias test in a periampullary cancer WGS study (DUOAC/AMPAC/CAC) PMID:26804919
  • RECQL4 observed as a low-frequency hit (>=2 ATC or >=3 PDTC) in a targeted-sequencing study of advanced thyroid cancers (PDTC and ATC). PMID:26878173

Cancer types (linked)

  • Anaplastic thyroid carcinoma (THAP) — RECQL4 germline variants in 5% of ATC patients; the most common germline cancer predisposition finding in the GATCI multi-institutional ATC cohort PMID:38412093.

Co-occurrence and mutual exclusivity

  • RECQL4 germline variants co-occur with somatic ATC driver mutations (TP53, BRAF, PIK3CA, CDKN2A, RB1) in the same tumors; the germline RECQL4 hit may represent a cancer-predisposing background alteration PMID:38412093.

Therapeutic relevance

  • RECQL4 loss impairs DNA repair; RECQL4-deficient tumors may be sensitized to DNA-damaging agents or PARP inhibitors (by analogy with other helicase-deficient cancers), though this has not been directly tested in ATC PMID:38412093.

Open questions

  • Whether RECQL4 germline variants represent a true cancer predisposition syndrome for ATC or are incidental findings requires larger germline-cancer association studies.
  • The functional consequence of specific RECQL4 variants detected in the GATCI cohort (germline pathogenicity classification) was not reported in detail.

Sources

This page was processed by crosslinker on 2026-04-11. - PMID:26804919

This page was processed by wiki-cli on 2026-05-14. - PMID:26878173

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