{"entity":{"id":"paper-schoenfeld-smarca4-alterations-lung-ccr-2020","kind":"paper","name":"The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer","aka":[],"tldr":"One of the most commonly mutated genes in lung cancer turns out to come in two kinds: one that destroys the protein and carries the worst prognosis, and one that leaves it intact. Both do worse than average, and both do better than average on immunotherapy.","summary":"Genomic, protein expression and clinical outcome data were analysed for patients with SMARCA4-altered lung cancer treated at one centre. Among 4,813 patients with non-small-cell lung cancer, 407, 8%, carried a SMARCA4 alteration. Two categories were described: class 1 (truncating mutations, fusions and homozygous deletion) and class 2 (missense mutations). Loss of protein expression was associated with class 1 alterations, 81% against 0%. Both classes co-occurred more frequently with KRAS, STK11 and KEAP1 mutations than in SMARCA4 wild-type tumours. In metastatic disease, SMARCA4 alterations were associated with shorter overall survival, with class 1 the shortest. Treatment with immune checkpoint inhibitors was associated with improved outcomes in SMARCA4-altered tumours, with class 1 responding best.","asOf":"2026-09-25","links":[{"label":"Schoenfeld et al., Clin Cancer Res 2020: the genomic landscape of SMARCA4 alterations in 4,813 lung cancers","url":"https://doi.org/10.1158/1078-0432.CCR-20-1825"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32709715/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["cgp","histopathology-ihc","checkpoint-inhibitor"],"targets":["smarca4","kras","stk11","keap1"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["swi-snf-chromatin","t-cell-exhaustion"],"terms":["driver-mutation","vus","ihc","stk11-keap1"],"trials":[],"people":["gregory-riely"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2020,"doi":"10.1158/1078-0432.CCR-20-1825","pmid":"32709715","authors":"Schoenfeld AJ, Bandlamudi C, Lavery JA, et al.","paperType":"observational","findings":["SMARCA4 alterations in 407 of 4,813 lung cancers, 8%, in two genomically and clinically distinct classes.","Protein loss in 81% of class 1 alterations and none of class 2.","Both classes co-occur with KRAS, STK11 and KEAP1 and are independent predictors of poor prognosis.","Checkpoint inhibitor outcomes were better in SMARCA4-altered tumours, class 1 best."],"whatItMeans":"It turned a frequently reported variant into an interpretable one: the class decides whether the stain will be negative, how poor the prognosis is, and whether immunotherapy is more rather than less likely to help.","caveats":["Single centre and retrospective.","Immunotherapy comparison is not randomised and is confounded by co-mutation.","Class 2 missense variants include variants of unknown significance."],"changedPractice":false,"participants":4813},"route":"/key-papers/paper-schoenfeld-smarca4-alterations-lung-ccr-2020/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"keap1","kind":"target","name":"KEAP1","route":"/targets/keap1/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"smarca4","kind":"target","name":"SMARCA4","route":"/targets/smarca4/"},{"id":"stk11","kind":"target","name":"STK11","route":"/targets/stk11/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"swi-snf-chromatin","kind":"pathway","name":"SWI/SNF chromatin remodelling","route":"/pathways/swi-snf-chromatin/"},{"id":"t-cell-exhaustion","kind":"pathway","name":"T-cell exhaustion","route":"/pathways/t-cell-exhaustion/"}],"term":[{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"},{"id":"stk11-keap1","kind":"term","name":"STK11 / KEAP1 co-mutations","route":"/terms/stk11-keap1/"},{"id":"vus","kind":"term","name":"Variant of uncertain significance (VUS)","route":"/terms/vus/"}],"person":[{"id":"gregory-riely","kind":"person","name":"Gregory J. Riely","route":"/people/gregory-riely/"}],"journal":[{"id":"clinical-cancer-research","kind":"journal","name":"Clinical Cancer Research","route":"/journals/clinical-cancer-research/"}]}}