{"entity":{"id":"paper-bergethon-ros1-rearrangements-lung-jco-2012","kind":"paper","name":"ROS1 rearrangements define a unique molecular class of lung cancers","aka":[],"tldr":"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.","asOf":"2026-09-25","links":[{"label":"Bergethon et al., J Clin Oncol 2012: ROS1 rearrangements define a unique molecular class of lung cancers (1,073 screened)","url":"https://doi.org/10.1200/JCO.2011.35.6345"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22215748/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cytogenetics-fish","kinase-inhibitors"],"targets":["ros1","alk"],"drugs":["crizotinib"],"companies":[],"institutions":["mgh"],"pathways":["rtk-activation"],"terms":["gene-fusion","driver-mutation","fish"],"trials":[],"people":["alice-shaw"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2012,"doi":"10.1200/JCO.2011.35.6345","pmid":"22215748","authors":"Bergethon K, Shaw AT, Ou SH, et al.","paperType":"translational","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."],"whatItMeans":"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."],"changedPractice":true,"participants":1073},"route":"/key-papers/paper-bergethon-ros1-rearrangements-lung-jco-2012/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","route":"/technologies/cytogenetics-fish/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"},{"id":"ros1","kind":"target","name":"ROS1","route":"/targets/ros1/"}],"drug":[{"id":"crizotinib","kind":"drug","name":"Crizotinib","route":"/drugs/crizotinib/"}],"institution":[{"id":"mgh","kind":"institution","name":"Massachusetts General Hospital Cancer Center","route":"/institutions/mgh/"}],"pathway":[{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"term":[{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"}],"person":[{"id":"alice-shaw","kind":"person","name":"Alice T. Shaw","route":"/people/alice-shaw/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}],"biomarker":[{"id":"ros1-fusion","kind":"biomarker","name":"ROS1 fusion (ROS1-positive)","route":"/biomarkers/ros1-fusion/"}]}}