Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Sep;47(9):1003-10.
doi: 10.1038/ng.3375. Epub 2015 Aug 10.

Genomic spectra of biliary tract cancer

Hiromi Nakamura  1 , Yasuhito Arai  1 , Yasushi Totoki  1 , Tomoki Shirota  1   2 , Asmaa Elzawahry  1 , Mamoru Kato  3 , Natsuko Hama  1 , Fumie Hosoda  1 , Tomoko Urushidate  4 , Shoko Ohashi  1 , Nobuyoshi Hiraoka  5 , Hidenori Ojima  5   6 , Kazuaki Shimada  7 , Takuji Okusaka  8 , Tomoo Kosuge  7 , Shinichi Miyagawa  2 , Tatsuhiro Shibata  1   4
Affiliations

Genomic spectra of biliary tract cancer

Hiromi Nakamura et al. Nat Genet. 2015 Sep.

Abstract

The incidence of biliary tract cancer (BTC), including intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma and gallbladder cancer, has increased globally; however, no effective targeted molecular therapies have been approved at the present time. Here we molecularly characterized 260 BTCs and uncovered spectra of genomic alterations that included new potential therapeutic targets. Gradient spectra of mutational signatures with a higher burden of the APOBEC-associated mutation signature were observed in gallbladder cancer and ECC. Thirty-two significantly altered genes, including ELF3, were identified, and nearly 40% of cases harbored targetable genetic alterations. Gene fusions involving FGFR2 and PRKACA or PRKACB preferentially occurred in ICC and ECC, respectively, and the subtype-associated prevalence of actionable growth factor-mediated signals was noteworthy. The subgroup with the poorest prognosis had significant enrichment of hypermutated tumors and a characteristic elevation in the expression of immune checkpoint molecules. Accordingly, immune-modulating therapies might also be potentially promising options for these patients.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 - PubMed
    1. Nat Rev Cancer. 2012 Mar 22;12(4):237-51 - PubMed
    1. Science. 2014 Feb 28;343(6174):1010-4 - PubMed
    1. Gastroenterology. 2013 Dec;145(6):1215-29 - PubMed
    1. Nature. 2014 Nov 27;515(7528):568-71 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources