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Genetics

Genetics of biliary tract cancer

Nature Reviews Gastroenterology & Hepatology volume 10, page 692 (2013)Cite this article

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Two new studies have used next-generation whole-exome sequencing to reveal a potential key role for chromatin remodelling in the development of cholangiocarcinoma. The findings, reported in Nature Genetics, provide new clues to the underlying biology of biliary tract cancers and highlight new therapeutic targets, a crucial step forward given that no effective therapies other than surgery are currently available.

In the first study, Laura Wood and colleagues performed whole-exome sequencing on 32 intrahepatic cholangiocarcinomas and nine gallbladder carcinomas in a bid to identify alterations that drive tumour formation. The researchers identified nearly 2,000 somatic mutations, and found that three chromatin-remodelling genes in particular—BAP1, ARID1A and PBRM1—potentially had a role in the development of intrahepatic cholangiocarcinoma. “Together, these genes were mutated in almost half of the cancers sequenced, and their mutations were strongly enriched for inactivating mutations, pointing to their role as tumour suppressors,” notes Wood.

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References

  1. Jiao, W. et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat. Genet. 10.1038/ng.2813

  2. Chan-on, W. et al. Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat. Genet. 10.1038/ng.2806

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  1. Katrina Ray
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Ray, K. Genetics of biliary tract cancer. Nat Rev Gastroenterol Hepatol 10, 692 (2013). https://doi.org/10.1038/nrgastro.2013.219

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