117P - Genomic landscape of biliary tract cancers from India show distinct geographic variation

Background

Biliary tract cancers (BTC) are a group of heterogeneous tumors that include intrahepatic, perihilar, and distal cholangiocarcinoma and gall bladder cancers (1). India has a high burden of biliary tract tumors, particularly gallbladder cancers. It contributes to 10% of global burden of gall bladder cancers. Within India, the Indo-Gangetic doab has a higher incidence of BTCs of 21/100,000 individuals affected (2). Cholangiocarcinoma and gall bladder cancers have distinct genomic diversity (3). Genomic profiling of BTCs from India are scarce. Understanding of genomic diversity of BTCs in India shall help in strategizing therapy and prevention. Aim The main objectives of the study are: 1. Retrospective analysis of genomic profile of biliary tract cancers from India 2. Pathway analysis of BTCs based on genomic profiling.

Methods

46 BTC cases from India were recruited for the study spanning 10 centers across India. All the cases were tested using comprehensive genomic profiling under Foundation One CDx or Foundation One Liquid CDx assay. Only the genomic results were used for retrospective analysis.

Results

33 cases of cholangiocarcinoma and 13 cases of gallbladder cancers were analyzed. The most commonly altered genes in cholangiocarcinoma were TP53 (45%), CDKN2A/B (33%), ARID1A (21%), KRAS (21%). The most commonly altered genes in gallbladder were TP53 (77%), CDKN2A/B (31%), RB1 (23%) and SMAD4 (23%). Pathway analysis showed a distinct difference between cholangiocarcinoma and gallbladder tumors. Transcriptional factors and Immune-modifier pathways were enriched in gallbladder tumors compared to cholangiocarcinoma, while the cell cycle pathway was more commonly altered in cholangiocarcinoma. When the cholangiocarcinoma cases were stratified by demographic origin within India, we found cell cycle pathway genes to be significantly less among North Indian samples, while RAS-RAF pathway was significantly more among North Indian samples.

Conclusions

The genomic landscape of BTCs in India showed distinct variation compared to the rest of the world. A trend of variation in the genomic landscape of BTCs between North & South India was observed. Further study with higher sample size is warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Kumar: Financial Interests, Personal, Other, Author is an employee of Roche Products India Pvt Ltd.: Roche Products India Pvt Ltd. All other authors have declared no conflicts of interest.