{"entity":{"id":"paper-narayan-gallbladder-regional-mutations-cancer-2019","kind":"paper","name":"Regional differences in gallbladder cancer pathogenesis: insights from a multi-institutional comparison of tumor mutations","aka":[],"tldr":"Comparing gallbladder tumours from Chile, Japan and the United States, Japanese patients were older with fewer stone-related cancers and different mutations, while SMAD4 loss was common everywhere and went with shorter survival.","summary":"Primary tumours from 81 patients with gallbladder cancer treated in Chile (21), Japan (11) and the United States (49) between 1999 and 2016 underwent targeted sequencing of known cancer-associated genes. Japanese patients were older (median 72 years versus 59 in Chile and 66 in the United States), had more well-differentiated tumours (46% versus 0%) and fewer gallstone-associated cancers (36% versus 67% and 69%), and had a higher median mutation burden (6 versus 7 in Chile and 4 in the United States; P = 0.006).\n\nTumours from Japanese patients lacked ARID1A and PIK3CA mutations, whereas Chilean tumours lacked ERBB3 and ARID2 mutations. SMAD4 was mutated similarly across centres (38% in Chile, 36% in Japan, 27% in the United States) and was univariately associated with worse overall survival (median 10 versus 25 months; P = 0.039). At least one potentially actionable gene was altered in 80% of tumours.","asOf":"2026-09-24","links":[{"label":"Narayan et al., Cancer 2019: regional differences in gallbladder cancer mutations (Chile, Japan, United States)","url":"https://doi.org/10.1002/cncr.31850"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30427539/"},{"label":"cBioPortal study gbc_msk_2018 (Gallbladder Cancer, MSK, Cancer 2018; 103 samples)","url":"https://www.cbioportal.org/study/summary?id=gbc_msk_2018"}],"tags":[],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":["smad4","arid1a","pik3ca","her3","arid2"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":["ghassan-abou-alfa"],"bottlenecks":[],"keyPapers":[],"journals":["cancer-wiley"],"dependsOn":[],"notes":[],"journal":"Cancer","year":2019,"doi":"10.1002/cncr.31850","pmid":"30427539","authors":"Narayan RR, Creasy JM, Goldman DA, et al.","paperType":"observational","findings":["SMAD4 mutated in 38% (Chile), 36% (Japan) and 27% (United States); median survival 10 versus 25 months with and without it.","Japanese tumours lacked ARID1A and PIK3CA mutations; Chilean tumours lacked ERBB3 and ARID2.","At least one potentially actionable alteration in 80% of tumours."],"whatItMeans":"Regional biology is real but partial: exposures and age differ, some genes differ, and SMAD4 loss emerges as the shared bad-prognosis marker. It is the paper behind the MSK 2018 gallbladder study on cBioPortal (gbc_msk_2018).","caveats":["Only 11 Japanese and 21 Chilean tumours; absence of a mutation in such small groups is weak evidence.","Targeted panel, so tumour mutation burden is a panel count, not a per-megabase figure."],"changedPractice":false,"participants":81},"route":"/key-papers/paper-narayan-gallbladder-regional-mutations-cancer-2019/","neighbours":{"cancer":[{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"}],"target":[{"id":"arid1a","kind":"target","name":"ARID1A","route":"/targets/arid1a/"},{"id":"arid2","kind":"target","name":"ARID2","route":"/targets/arid2/"},{"id":"her3","kind":"target","name":"HER3","route":"/targets/her3/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"},{"id":"smad4","kind":"target","name":"SMAD4","route":"/targets/smad4/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"person":[{"id":"ghassan-abou-alfa","kind":"person","name":"Ghassan K. Abou-Alfa","route":"/people/ghassan-abou-alfa/"}],"journal":[{"id":"cancer-wiley","kind":"journal","name":"Cancer","route":"/journals/cancer-wiley/"}]}}