Abstract 3437: Genomic alterations, mutation burden, and microsatellite instability status of Chinese intrahepatic cholangiocarcinoma

Abstract

Abstract Background: Intrahepatic cholangiocarcinoma (ICC) is often diagnosed at an advanced stage with limited therapeutic options and poor prognosis. Targeted and immune-therapy have yielded promising therapeutic effects in various solid tumor patients (pts). Thus the understanding of ICC genomic profiling, especially which of Chinese pts, seems to be necessary for the treatment strategy for ICC. Methods: Comprehensive genomic profiling of molecular alterations and predictive biomarkers to personalized treatment genes were performed on Formalin Fixed Paraffin Embedded (FFPE) samples and matched blood samples of 69 Chinese ICC pts. Genomic alterations (GAs) including substitutions, short and long insertion/deletions (indels), copy number variations and gene rearrangements were assessed. Tumor mutation burden (TMB) of total somatic substitutions and indels per megabase after filtering known driver mutations was calculated. Microsatellite instability (MSI) status was determined by identifying and scoring multiple mono-nucleotide repeats loci. Results: Median age of the 69 ICC pts was 58 years (range: 38-88), and male vs female was approximately 3:1. Average of 3.7 GAs /sample and 0.9 actionable GAs/sample were detected. The most widespread genomic alterations among the pts were revealed as TP53 (44.9%), ARIDIA (23.2%), KRAS (18.8%), BAP1 (14.5%), IDH1/2 (14.5%), PIK3CA (11.6%), FGFR2/3 (10.1%), MLC1 (8.7%), CDKN2A/B (8.7%), BRAF (7.2%), TERT (7.2%), PBRM1 (7.2%). The actionable mutations of the PI3K/mTOR pathway were found in 18.8% of the pts. In total, pts with one or more actionable GAs were 62.3%. Pts presented MSI-high were 7.2% of the total. Proportion was 10.1% for the pts with TMB value higher than 20 mut/Mb, and 32.8% for those higher than 10 mut/Mb. The TMB range of the 69 pts was 1.1 to 58.4 mut/Mb, and median was 7.4 mut/Mb. Conclusions: In our study, 62.3% of Chinese ICC pts were detected to have actionable GAs which could potentially guide and influence their personalized treatments. The identification of more frequent high TMB level than the published western populations indicated that Chinese ICC pts may more likely derive therapeutic benefits from immune checkpoint inhibitors. Citation Format: Jingyu Cao, Bo Jiang, Zimin Liu, Weibin Shu, Lei Li, Han Yang, Hua Li, Zhiyu Xiao, Maolin Yan, Jie Lin, Siqin Liu, Peng Zhang, Milind Javle, Ming Yao, Kai Wang, Haitao Zhao. Genomic alterations, mutation burden, and microsatellite instability status of Chinese intrahepatic cholangiocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3437.