Biliary tract cancer (BTC) is a heterogeneous group of cancers, including gallbladder cancer and extrahepatic and intrahepatic cholangiocarcinoma. BTC has been known as a disease with a poor prognosis, with few treatment options, regardless of its low incidence. In Korea, in 2014, the crude incidence rate of BTC was 11.2 per 100,000 men, and the crude mortality rate was 7.7 per 100,000 in both men and women [1]. Most patients have been diagnosed at an advanced stage. Although surgical resection is a curative treatment, recurrence of disease has been a clinical issue for patients after surgery [2]. Combination treatment with cisplatin plus gemcitabine has been reported as an appropriate treatment for patients with advanced BTC [3].

The genomic characteristics of BTC have been revealed through several studies using high-throughput next-generation sequencing technologies [4–6]. Jiao et al. [5] reported exome sequencing results of 32 patients with intrahepatic cholangiocarcinoma. Inactivating mutations in chromatin remodeling genes, including BAP1, ARID1A, and PBRM1, were identified with frequent mutations in IDH1 and IDH2. The oncogenes KRAS, PIK3CA, NRAS, GNAS, and ERBB2 were also significantly mutated in BTC [6]. Genomic analyses need to be performed in more BTCs to understand their biology and develop therapeutic strategies.

Here, we reported the whole-exome sequencing (WES) data of seven patients with BTC and analyzed their somatic mutations to compare the genetic features between patients.

The demographic and clinical characteristics of the patients with BTC, including age, sex, cancer stage, recurrence, and survival, are summarized in Table 1.

The patients included three females and four males with an average age of 60 years. Among the seven patients, five patients were defined as experiencing recurrence of disease after surgery.

We analyzed whole-exome sequencing data of matched tumor and normal DNA from the patients. The mean coverage depth for all samples is demonstrated in Supplementary Table 1. In total, 274 somatic mutations in protein-coding regions were called by both callers, Strelka and Mutect. The average number of somatic mutations per case was 34, showing a range of 25 to 59 (Fig. 1). We found two patients harboring activating mutations in KRAS, such as G12V and G13D (Table 2). Missense mutations in codon 61 of the NRAS gene and codon 766 of the NTRK1 gene were also detected in two patients. A nonsense mutation in TP53 was found in a patient, and APC was inactivated by frameshift mutations in two patients. A patient harbored a frameshift mutation that was caused by a deletion of G in the ARID1A gene. Detailed information on the somatic mutations is provided in Supplementary Table 2.

This study analyzed somatic mutations using WES in a limited number of patients with BTC. To understand the genetic features of BTC, more data need to be analyzed from more patients.

Supplementary data including two tables can be found with this article online at https://doi.org/10.5808/GI.2018.16.4.e35.