# ROS1 rearrangements define a unique molecular class of lung cancers

Source: https://onco.cc/key-papers/paper-bergethon-ros1-rearrangements-lung-jco-2012/  
OnCo record `paper-bergethon-ros1-rearrangements-lung-jco-2012` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Screening more than a thousand lung cancers found a rearranged ROS1 gene in about one in sixty, in younger patients who had mostly never smoked, and the first patient treated with a matched pill nearly cleared her cancer.

## Summary

A fluorescence in situ hybridisation assay was used to screen 1,073 patients with non-small-cell lung cancer, and rearrangement status was correlated with clinical characteristics, overall survival and ALK status. Eighteen tumours, 1.7%, were ROS1-rearranged and 31, 2.9%, were ALK-rearranged. Compared with the ROS1-negative group, ROS1-rearranged patients were significantly younger and more likely to be never smokers, all tumours were adenocarcinomas with a tendency towards higher grade, and overall survival did not differ. A ROS1-rearranged cell line and cells transfected with CD74-ROS1 were sensitive to crizotinib, and one patient treated in an expanded phase 1 cohort showed tumour shrinkage approaching a complete response.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Journal of Clinical Oncology
- Year: 2012
- DOI: 10.1200/JCO.2011.35.6345
- Authors: Bergethon K, Shaw AT, Ou SH, et al.
- Findings: ROS1 rearrangement in 18 of 1,073 lung cancers, 1.7%, against ALK in 31, 2.9%.; Patients were younger and more often never smokers; all tumours were adenocarcinomas.; Overall survival did not differ by ROS1 status.; Laboratory and first-patient evidence of crizotinib sensitivity.
- What it means: It defined a class of lung cancer by a rearrangement and a clinical phenotype at the same time, and it is the reason ROS1 testing is recommended for every patient with adenocarcinoma rather than only for those with an obvious risk profile.
- Caveats: Eighteen positive cases, so the clinical description rests on few patients.; Fluorescence in situ hybridisation does not identify the fusion partner, which matters for inhibitor choice.; The treatment evidence at the time was a single patient.

## Sources

- Bergethon et al., J Clin Oncol 2012: ROS1 rearrangements define a unique molecular class of lung cancers (1,073 screened): https://doi.org/10.1200/JCO.2011.35.6345
- PubMed: https://pubmed.ncbi.nlm.nih.gov/22215748/

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Cytogenetics and FISH](https://onco.cc/technologies/cytogenetics-fish/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ALK](https://onco.cc/targets/alk/), [ROS1](https://onco.cc/targets/ros1/)
- drugs: [Crizotinib](https://onco.cc/drugs/crizotinib/)
- institutions: [Massachusetts General Hospital Cancer Center](https://onco.cc/institutions/mgh/)
- pathways: [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- terms: [Driver mutation](https://onco.cc/terms/driver-mutation/), [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [Gene fusion](https://onco.cc/terms/gene-fusion/)
- people: [Alice T. Shaw](https://onco.cc/people/alice-shaw/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)
- biomarkers: [ROS1 fusion (ROS1-positive)](https://onco.cc/biomarkers/ros1-fusion/)

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