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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.
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).
Tumours 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.
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).
Shares Cancer, ARID1A, SMAD4, Gallbladder cancer.
Shares Ghassan K. Abou-Alfa, SMAD4, Memorial Sloan Kettering Cancer Center, Gallbladder cancer.
Shares Ghassan K. Abou-Alfa, SMAD4, PIK3CA / PI3K-alpha, Memorial Sloan Kettering Cancer Center.
Shares ARID1A, SMAD4, PIK3CA / PI3K-alpha, Gallbladder cancer.
Shares Ghassan K. Abou-Alfa, Memorial Sloan Kettering Cancer Center, Gallbladder cancer.
Shares ARID1A, SMAD4, Gallbladder cancer.
Shares ARID1A, SMAD4, Gallbladder cancer.