Exome sequencing of 22 genes using tissue from patients with biliary tract cancer

Abstract

Biliary tract cancers (BTC) are a rare heterogeneous disease group with a dismal prognosis and limited treatment options. The mutational landscape consists of genetic aberrations both shared by and characteristic for anatomical location. Here, we present exome sequencing data on 22 genes from a phase 2 trial using a clinically validated panel used in patients with colorectal cancer. A total of 56 patients were included in a one‐armed phase 2 trial investigating the treatment combination of capecitabine, gemcitabine, oxaliplatin, and cetuximab. Tissue DNA yield and quality allowed analysis of 30 patients on our panel including 22 genes. ARID1A (33%) and TP53 (33%) were found to be most frequently mutated followed by KRAS mutations found in 20% of the patients. Mutational aberrations in ARID1A were found more prevalent than expected, whereas TP53 and KRAS were in concordance with earlier reported data. Mutation in CTNNB1 was significantly associated with poor prognosis. Our panel is clinically validated and suitable for a high volume of samples to detect mutations in patients with BTC. However, it is reasonable to assume that the clinical utility could be optimized in this patient group by extending the panel to include BTC specific mutations with potential therapeutic consequences such as IDH1/2, FGFR fusions, ERBB3, and BRCA1/2.

An Integrative Analysis Reveals the Underlying Association Between CTNNB1 Mutation and Immunotherapy in Hepatocellular Carcinoma

“…An activating mutation in exon 3 of CTNNB1 results in accumulation of β-catenin in the nucleus and activates the transcription of downstream target gene such as lymphoid enhancer-binding factor 1 (LEF1) (17), and LEF1 is a transcription factor that has been implicated in the pathogenesis of multiple tumors (18). It has been reported that CTNNB1 mutation was highly associated with many kinds of human tumors, such as biliary tract cancer (19), lung adenocarcinoma (20), and endometrioid ovarian carcinoma (21). In our research, CTNNB1 mutation was significantly associated with a better prognosis and a higher TMB.…”

Clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma

“…By sorting the frequency of mutations in patients, they got eight commonly mutated genes in intrahepatic and extrahepatic cholangiocarcinoma including IDH1, TP53, ARID1A, BAP1, KRAS, PBRM1, SMAD4 and ATM. Besides, there was also a 30-patients study comparing different types of biliary tract cancer with a 22gene panel by Hogdall et al [5]. They identified three significantly mutated genes including ARID1A, TP53, and KRAS in CCA (cholangiocarcinoma).…”

Clinically significant shared and distinct genomic alterations in Chinese and Western patients with intrahepatic cholangiocarcinoma

“…By sorting the frequency of mutations in patients, they got another eight commonly mutated genes in intrahepatic and extrahepatic cholangiocarcinoma including IDH1, TP53, ARID1A, BAP1, KRAS, PBRM1, SMAD4 and ATM. Besides, there was also a 30-patients study comparing different types of biliary tract cancer with a 22gene panel by Hogdall et al (2020). They identi ed three signi cantly mutated genes including ARID1A, TP53, and KRAS in CCA (cholangiocarcinoma).…”