TY - JOUR

T1 - Exome sequencing of 22 genes using tissue from patients with biliary tract cancer

AU - Høgdall, Dan

AU - Larsen, Ole F

AU - Linnemann, Dorte

AU - Svenstrup Poulsen, Tim

AU - Høgdall, Estrid V

N1 - © 2019 APMIS. Published by John Wiley & Sons Ltd.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Antineoplastic Agents/therapeutic use

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Bile Duct Neoplasms/drug therapy

KW - Cohort Studies

KW - Exome

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Mutation

KW - Nuclear Proteins/genetics

KW - Paraffin Embedding

KW - Prognosis

KW - Proto-Oncogene Proteins p21(ras)/genetics

KW - Sequence Analysis, DNA

KW - Transcription Factors/genetics

KW - Tumor Suppressor Protein p53/genetics

KW - beta Catenin/genetics

U2 - 10.1111/apm.13003

DO - 10.1111/apm.13003

M3 - Journal article

C2 - 31628675

VL - 128

SP - 3

EP - 9

JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica

JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica

SN - 0903-4641

IS - 1

ER -