143IN - Potentially druggable gene alterations in gastrointestinal cancer

Date 28 September 2014
Event ESMO 2014
Session ESMO-JSMO: How to integrate genome sequencing data in oncology
Topics Personalised Medicine
Translational Research
Presenter Mamoru Kato
Citation Annals of Oncology (2014) 25 (suppl_4): iv50-iv50. 10.1093/annonc/mdu323
Authors M. Kato
  • Department Of Bioinformatics, National Cancer Center, 104-0045 - Tokyo/JP

Abstract

Body

Abstract:

Liver cancer is the third leading cause of cancer-related death worldwide. This category includes hepatocellular carcinoma (HCC) and intra-hepatic cholangiocarcinoma (ICC). Recent advances in sequencing technologies have enabled us to decode the liver cancer genomes at the highest resolution and to identify novel genetic alterations including therapeutic targets. To understand the genetic basis for HCC, international collaboration between Japan and US groups has launched and achieved to collect more than 500 HCC exome data. Based on somatic mutations and copy number alterations identified in this cohort, we have uncovered potential therapeutic targets, including growth factor signalling/kinases, WNT, TERT, and chromatin modifying factors. Furthermore, we could map the signaling modules operating in the HCC genomes. These analyses should also provide the way for new genotype-oriented molecular classifications for clinical application. ICC, another type of liver cancer, is frequent in the East-Asian population, but rare in the Western countries. Identification of therapeutic targets in this tumor has been slow, and therefore no molecular-target therapy has been approved so far. We and other groups recently performed RNA sequencing of primary ICC cases and reported recurrent FGFR2 fusion genes. NIH3T3 cells containing FGFR2 fusions showed oncogenic activities, which were suppressed by small molecule FGFR inhibitors. These FGFR2 fusion genes are considered as druggable driver genes in ICC and clinical examination of anti-FGFR therapies could be warranted in FGFR2-fusion positive ICC cases.

Disclosure:

The author has declared no conflicts of interest.