Genomic landscape of cholangiocarcinoma in India: ethnic variants and implications for targeted therapy
The study reveals region‑specific genomic alterations in Indian cholangiocarcinoma, including elevated TP53/KRAS mutations and a distinctive non‑fusion FGFR2 alteration pattern.
This retrospective, multi‑institutional study analyzed 220 cholangiocarcinoma (CCA) cases from India, profiling 42 shared DNA and 13 RNA NGS genes across four validated platforms. TP53, KRAS, IDH1 and PIK3CA were the most frequently mutated genes in unclassified CCA (35.6 %, 19.4 %, 10.2 % and 9.4 % respectively). Compared with international cBioPortal datasets, the Indian cohort showed significantly higher TP53 (35.8 % vs. 24.2 %), KRAS (19.4 % vs. 13.0 %), and PIK3CA (9.4 % vs. 4.1 %) mutations, but lower BAP1 (5.0 % vs. 13.2 %). A distinctive pattern of non‑fusion FGFR2 alterations (8 alterations: 3 pathogenic mutations, 3 copy‑number amplifications, 1 VUS) was identified, contrasting with the global FGFR2 fusion‑driven landscape. Tumor mutation burden was predominantly low; microsatellite instability‑high was rare (1 of 29, 3.4 %). The findings underscore region‑specific genomic drivers and highlight the need for population‑specific precision oncology studies in India.
These ethnicity‑stratified findings underscore the importance of population‑specific genomic profiling for precision oncology and may inform targeted therapeutic strategies for Indian patients.
Bizonyítékszint: Állatkísérletes. Állatmodellben vizsgálták.
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