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The largest Indian series, 376 patients sequenced at three centres, found the disease strikes a decade earlier than elsewhere, with TP53 and HER2 the leading changes and immunotherapy markers rare.
376 patients with gallbladder carcinoma (339 tissue and 37 plasma cell-free DNA samples) from three Indian institutions (2022 to 2024) were analysed with clinically validated next-generation sequencing panels and compared with Western, Asian and multi-ethnic cohorts curated from cBioPortal. The disease was more frequent in women (1.5 to 1) and diagnosed nearly a decade earlier than in international cohorts (median age 54).
TP53 (54%) and ERBB2 (15%; approximately 8% amplification, with S310F/Y hotspot predominance) were the most common alterations, followed by CDKN2A (9%), KRAS (7%) and SMAD4 (7%). Microsatellite instability-high (0.6%, 2 of 170 tested) and tumour mutational burden-high (1.3%, 1 of 79 tested) were rare. Indian patients had significantly lower ARID1A, SMAD4 and CDKN2A alteration rates than Western and Asian cohorts (all P < 0.001). Of 37 cfDNA patients, 13 showed no variants, but detected alterations qualitatively mirrored tissue.
HER2 is as frequent in India as in the West, so HER2 testing pays off in the highest-incidence population, while tumour-agnostic immunotherapy markers will rarely apply. The paper also shows plasma testing is feasible where tissue is scarce.
Shares TMB-high (tumour mutational burden >= 10 mutations per megabase), SMAD4, MSI-high (microsatellite instability by PCR or sequencing), CDKN2A.
Shares TMB-high (tumour mutational burden >= 10 mutations per megabase), SMAD4, CDKN2A, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2).
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Tumour mutational burden (TMB), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), HER2.
Shares TMB-high (tumour mutational burden >= 10 mutations per megabase), Tumour mutational burden (TMB), TP53, Gallbladder cancer.
Shares HER2 (ERBB2) activating mutation, HER2 testing in biliary tract cancer (IHC, ISH and NGS), HER2, Gallbladder cancer.
Shares MSI-high (microsatellite instability by PCR or sequencing), Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Gallbladder cancer.