Genomic spectra of biliary tract cancer

Hiromi Nakamura, Yasuhito Arai, Yasushi Totoki, Tomoki Shirota, Asmaa Elzawahry, Mamoru Kato, Natsuko Hama, Fumie Hosoda, Tomoko Urushidate, Shoko Ohashi, Nobuyoshi Hiraoka, Hidenori Ojima, Kazuaki Shimada, Takuji Okusaka, Tomoo Kosuge, Shinichi Miyagawa, Tatsuhiro Shibata

研究成果: Article

346 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1003-1010
ページ数8
ジャーナルNature Genetics
47
9
DOI
出版ステータスPublished - 2015 8 27

ASJC Scopus subject areas

  • Genetics

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