Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile

Author:

Ohyama Hiroshi123ORCID,Hirotsu Yosuke2,Amemiya Kenji2,Miura Yoshifumi1,Hirose Sumio3,Oyama Toshio4,Iimuro Yuji5,Kojima Yuichiro3,Mikata Rintaro1,Mochizuki Hitoshi23,Kato Naoya1,Omata Masao236

Affiliation:

1. Department of Gastroenterology Graduate School of Medicine Chiba University Chiba Japan

2. Genome Analysis Center Yamanashi Central Hospital Yamanashi Japan

3. Department of Gastroenterology Yamanashi Central Hospital Yamanashi Japan

4. Department of Pathology Yamanashi Central Hospital Yamanashi Japan

5. Department of Surgery Yamanashi Central Hospital Yamanashi Japan

6. University of Tokyo Tokyo Japan

Abstract

AbstractBackgroundObtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug‐matched mutations.MethodsThis study created a panel of 60 significantly mutated genes specific to pancreaticobiliary cancer (PBCA) and used it for genomic analysis of 212 deoxyribonucleic acid (DNA) samples (87 bile supernatant, 87 bile precipitate, and 38 plasma) from 87 patients with PBCA. The quantity of extracted DNA from bile and plasma was compared, as were genomic profiles of 38 pairs of bile and plasma from 38 patients with PBCA. Finally, we investigated 87 bile and 38 plasma for the ability to detect druggable mutations.ResultsThe amount of DNA was significantly lower in plasma than in bile (p < .001). Oncogenic mutations were identified in 21 of 38 (55%) patients in bile and nine (24%) in plasma samples (p = .005). Bile was significantly more sensitive than plasma in identifying druggable mutations (p = .032). The authors detected 23 drug‐matched mutations in combined bile and plasma, including five ERBB2, four ATM, three BRAF, three BRCA2, three NF1, two PIK3CA, one BRCA1, one IDH1, and one PALB2.ConclusionsLiquid biopsy using bile may be useful in searching for therapeutic agents, and using the obtained genomic information may improve the prognoses of patients with PBCA.Plain Language Summary Genomic profiling of formalin‐fixed paraffin‐embedded tissues may provide actionable targets for molecular and immuno‐oncological treatment. However, most pancreaticobiliary malignancies are unresectable and formalin‐fixed paraffin‐embedded tissues cannot be obtained. Although comprehensive genomic profiling tests using plasma have been used in recent years, the utility of those using bile is not clear. Our study revealed that bile identified more drug‐matched mutations than plasma in advanced pancreaticobiliary cancer patients. Bile may help widen the patient population benefiting from targeted drugs.

Funder

Japan Society for the Promotion of Science

Publisher

Wiley

Subject

Cancer Research,Oncology

Reference29 articles.

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