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

APMIS. 2020 Jan;128(1):3-9. doi: 10.1111/apm.13003.

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.

Keywords: Cholangiocarcinoma; NGS; biliary tract cancer; exome sequencing.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bile Duct Neoplasms / drug therapy
  • Bile Duct Neoplasms / genetics*
  • Cohort Studies
  • DNA-Binding Proteins
  • Exome*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Nuclear Proteins / genetics
  • Paraffin Embedding
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Sequence Analysis, DNA
  • Transcription Factors / genetics
  • Tumor Suppressor Protein p53 / genetics
  • beta Catenin / genetics

Substances

  • ARID1A protein, human
  • Antineoplastic Agents
  • CTNNB1 protein, human
  • DNA-Binding Proteins
  • KRAS protein, human
  • Nuclear Proteins
  • TP53 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • beta Catenin
  • Proto-Oncogene Proteins p21(ras)