# Genomic profiling of Indian gallbladder carcinoma: mutational insights in a high-incidence population

Source: https://onco.cc/key-papers/paper-suryavanshi-indian-gallbladder-genomics-jco-go-2025/  
OnCo record `paper-suryavanshi-indian-gallbladder-genomics-jco-go-2025` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: JCO Global Oncology
- Year: 2025
- DOI: 10.1200/go-25-00332
- Authors: Suryavanshi M, Ostwal V, Javle MM, et al.
- Findings: TP53 54%, ERBB2 15% (about 8% amplification; S310F/Y hotspot), CDKN2A 9%, KRAS 7%, SMAD4 7%.; MSI-high 0.6% (2 of 170) and TMB-high 1.3% (1 of 79).; ARID1A, SMAD4 and CDKN2A significantly less altered than in Western and Asian cohorts; median age at diagnosis 54.
- What it means: 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.
- Caveats: Heterogeneous panels across three institutions introduce variability in frequency estimates, as the authors state.; Retrospective series of patients who reached sequencing.

## Sources

- Suryavanshi et al., JCO Glob Oncol 2025: genomic profiling of 376 Indian gallbladder carcinomas: https://doi.org/10.1200/go-25-00332
- PubMed: https://pubmed.ncbi.nlm.nih.gov/41418080/

## Connected records

- cancers: [Gallbladder cancer](https://onco.cc/cancers/gallbladder/)
- targets: [ARID1A](https://onco.cc/targets/arid1a/), [CDKN2A](https://onco.cc/targets/cdkn2a/), [HER2](https://onco.cc/targets/her2/), [KRAS](https://onco.cc/targets/kras/), [Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)](https://onco.cc/targets/mmr/), [SMAD4](https://onco.cc/targets/smad4/), [TP53](https://onco.cc/targets/tp53/)
- institutions: [Tata Memorial Centre](https://onco.cc/institutions/tata-memorial/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [HER2 testing in biliary tract cancer (IHC, ISH and NGS)](https://onco.cc/terms/her2-testing-in-biliary-cancer/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/)
- biomarkers: [HER2 (ERBB2) activating mutation](https://onco.cc/biomarkers/her2-mutation/), [MSI-high (microsatellite instability by PCR or sequencing)](https://onco.cc/biomarkers/msi-high/), [TMB-high (tumour mutational burden >= 10 mutations per megabase)](https://onco.cc/biomarkers/tmb-high/)

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