ROS1

Overview

ROS1 encodes a receptor tyrosine kinase whose oncogenic fusions define a clinically actionable subgroup of non-small cell lung cancer, targetable by crizotinib, entrectinib, and other ROS1-directed inhibitors.

Alterations observed in the corpus

  • ROS1 rearrangements with diverse gene partners were detected in CSF ctDNA from lung carcinoma patients with CNS involvement, profiled by MSK-IMPACT in the csf_msk_2024 cohort (1,007 CSF samples, 711 patients) PMID:39289779.
  • ROS1 listed as a MAPK-pathway gene whose activating fusions are enriched in KRAS-WT / other-MAPK-mutant PDAC (activating MAPK fusions: 3.2% of KRAS-WT vs 0.04% of KRAS-mutant PDAC, P = 2 × 10⁻³⁵); ROS1 is one of the candidate fusion partners in this subtype. PMID:39753968
  • ROS1::PARK2 fusion (likely GOF) in 1 GBC patient PMID:36228155
  • ROS1 fusion in 7% of advanced NSCLC immunotherapy cohort; included in multivariate model for PFS PMID:36038778
  • Frameshift mutation (suspected germline) identified as a single-case alteration in sinonasal adenoid cystic carcinoma (AdCC) whole-exome/RNA-seq profiling PMID:24418857
  • Fusions in 4/230 (1.7%) LUAD cases (TCGA); exclusively in the transversion-low (TL) non-smoker subset (P = 1.85×10⁻⁴); enriched in the TRU transcriptional subtype. PMID:25079552
  • ROS1 fusions are an established therapeutic target in lung ADC; mentioned in the 1,144-tumor NSCLC landscape study in the context of RTK-directed therapies (ALK and ROS1 inhibitors) applying almost exclusively to lung ADC rather than lung SqCC, given the histology-restricted molecular landscape. PMID:27158780
  • ROS1 structural variants identified as interesting alterations in salivary duct carcinoma (SDCA) from a recurrent/metastatic head and neck NGS cohort PMID:27442865.
  • ROS1 fusions present in ~6–7% of young lung cancer patients (YLC) versus <2% in older NSCLC patients, making them significantly enriched in YLC PMID:27346245.
  • Fusions identified in LUAD; level 1 actionability with high matched-therapy uptake and clinical benefit; 2 ROS1-fusion patients died before crizotinib FDA approval (March 2016) for this indication PMID:28336552
  • Kinase fusions enriched in LUAD but also detected across 11 additional tumor types in 10,336 MSK-IMPACT cases; part of the targetable-alteration pool recovered by broad-panel sequencing vs amplicon panels PMID:28481359
  • Reported at 3% frequency in NSCLC with too few events for dedicated response analysis in the MSK-IMPACT anti-PD-(L)1 TMB cohort (n=240) PMID:29337640
  • Cited as a comparator oncogenic driver with approved targeted therapies achieving higher response rates than neratinib monotherapy in HER2-mutant solid tumors PMID:29420467

Cancer types (linked)

  • NSCLC — ROS1 fusions detected in CSF ctDNA from lung carcinoma patients with CNS tumors PMID:39289779.
  • Pancreatic adenocarcinoma (PAAD) — ROS1 activating fusions part of the MAPK-pathway alteration landscape enriched in KRAS-WT PDAC (other-MAPK-mutant subtype). PMID:39753968

Co-occurrence and mutual exclusivity

  • Not reported in the corpus.

Therapeutic relevance

  • ROS1 fusions are level 1 OncoKB actionable alterations in NSCLC; lung carcinomas had the highest clinical actionability rate among CSF ctDNA-positive samples in the MSK CSF cohort PMID:39289779.

Open questions

  • None flagged in the corpus.

Sources

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. - PMID:29420467

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