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Exome sequencing of 22 genes using tissue from patients with biliary tract cancer.
APMIS 2019A

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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 where in concordance with earlier reported data. Mutation in CTNNB1 was significantly associated with poor prognosis.

CONCLUSION

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.

Authors+Show Affiliations

Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. Biotech Research and Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Denmark.Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.Department of Pathology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev.Department of Pathology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev.Department of Pathology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31628675

Citation

Høgdall, Dan, et al. "Exome Sequencing of 22 Genes Using Tissue From Patients With Biliary Tract Cancer." APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica, 2019.
Høgdall D, Larsen OF, Linnemann D, et al. Exome sequencing of 22 genes using tissue from patients with biliary tract cancer. APMIS. 2019.
Høgdall, D., Larsen, O. F., Linnemann, D., Poulsen, T. S., & Høgdall, E. V. (2019). Exome sequencing of 22 genes using tissue from patients with biliary tract cancer. APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica, doi:10.1111/apm.13003.
Høgdall D, et al. Exome Sequencing of 22 Genes Using Tissue From Patients With Biliary Tract Cancer. APMIS. 2019 Oct 19; PubMed PMID: 31628675.
* Article titles in AMA citation format should be in sentence-case
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 - Poulsen,Tim Svenstrup, AU - Høgdall,Estrid V, Y1 - 2019/10/19/ PY - 2019/10/20/entrez KW - NGS KW - biliary tract cancer KW - cholangiocarcinoma KW - exome sequencing JF - APMIS : acta pathologica, microbiologica, et immunologica Scandinavica JO - APMIS N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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 where in concordance with earlier reported data. Mutation in CTNNB1 was significantly associated with poor prognosis. CONCLUSION: 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. SN - 1600-0463 UR - https://www.unboundmedicine.com/medline/citation/31628675/Exome_sequencing_of_22_genes_using_tissue_from_patients_with_biliary_tract_cancer L2 - https://doi.org/10.1111/apm.13003 DB - PRIME DP - Unbound Medicine ER -