ATR

Overview

ATR (ATM and Rad3-Related) is a serine/threonine kinase that senses and responds to replication stress and single-stranded DNA, coordinating the replication stress checkpoint. ATR mutations have been identified in anaplastic thyroid carcinoma (ATC) as part of a broader DNA damage response gene alteration landscape.

Alterations observed in the corpus

  • ATR is recurrently mutated in anaplastic thyroid carcinoma (ATC) in a multi-omic landscape study (WES/WGS of 87 specimens from 64 ATC and 28 paired differentiated thyroid cancer (DTC)) PMID:38412093.
  • Somatic mutations in 6.2% (4/65) of TNBC cases in a whole-genome sequencing study of 65 breast tumors (BCCRC cohort) PMID:22495314
  • Inactivating mutation contributing to G2/M checkpoint pathway alteration in transitional cell carcinoma (TCC) of the bladder PMID:24121792
  • Basally hyperphosphorylated in EWS::FLI1-expressing heMSCs but fails to further phosphorylate after etoposide; authors hypothesize EWS::FLI1-driven phosphatase activity (Ewing sarcoma cell-of-origin model) PMID:25186949
  • Cell-cycle/DNA-damage tumor suppressor with inactivating hits in cutaneous squamous cell carcinoma (29-tumor cSCC NGS cohort) PMID:25589618
  • ATR provides compensatory TRMT10A Ser28 phosphorylation when ATM is impaired; TRMT10A loss confers ATR-inhibitor sensitivity in prostate cancer cell lines PMID:28068672
  • ATR was among the antigen-presentation/immunology genes profiled in the OncoPrint of a 240-patient NSCLC cohort evaluating TMB as an ICI-response biomarker PMID:29337640.

Cancer types (linked)

  • THPA (anaplastic thyroid carcinoma) — ATR mutations are recurrent in ATC, preferentially mutated over paired DTC, suggesting a role in anaplastic transformation PMID:38412093.

Co-occurrence and mutual exclusivity

  • Co-occurs with other DNA damage response alterations (ATM, BRCA1, BRCA2) in ATC; these collectively rationalize investigation of PARP inhibitors PMID:38412093.

Therapeutic relevance

  • Recurrent DDR gene alterations (ATR, ATM, BRCA1, BRCA2) in ATC rationalize investigation of PARP inhibitors and ATR/ATM inhibitor combinations in this aggressive cancer type PMID:38412093.

Open questions

  • ATR inhibitors are not evaluated in ATC in the corpus; whether ATR-mutant ATCs represent a biomarker-selected population for replication-stress targeting requires prospective study PMID:38412093.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22495314

This page was processed by crosslinker on 2026-05-14. - PMID:24121792

This page was processed by crosslinker on 2026-05-14. - PMID:25186949

This page was processed by crosslinker on 2026-05-14. - PMID:25589618

This page was processed by crosslinker on 2026-05-14. - PMID:28068672

This page was processed by entity-page-writer on 2026-05-15. - PMID:29337640

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