4.7 Article

Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer

Journal

SCIENTIFIC REPORTS
Volume 5, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/srep18425

Keywords

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Funding

  1. National Cancer Center Research and Development Fund [25-A-3, 26-A-5]
  2. Takeda Science Foundation
  3. Ministry of Education, Science and Culture of Japan [26870874, 25134719, 26670613]
  4. Ministry of Health Labour and Welfare (Health and Labour Sciences Research Expenses for Commission and Applied Research for Innovative Treatment of Cancer)
  5. Medical Research Encouragement Prize of the Japan Medical Association
  6. National Cancer Center Research and Development Fund, Japan
  7. Grants-in-Aid for Scientific Research [25860432, 26870874, 26670613] Funding Source: KAKEN

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Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. The genomic landscape of the PDAC genome features four frequently mutated genes (KRAS, CDKN2A, TP53, and SMAD4) and dozens of candidate driver genes altered at low frequency, including potential clinical targets. Circulating cell-free DNA (cfDNA) is a promising resource to detect and monitor molecular characteristics of tumors. In the present study, we determined the mutational status of KRAS in plasma cfDNA using multiplex picoliter-droplet digital PCR in 259 patients with PDAC. We constructed a novel modified SureSelect-KAPA-Illumina platform and an original panel of 60 genes. We then performed targeted deep sequencing of cfDNA and matched germline DNA samples in 48 patients who had >= 1% mutant allele frequencies of KRAS in plasma cfDNA. Importantly, potentially targetable somatic mutations were identified in 14 of 48 patients (29.2%) examined by targeted deep sequencing of cfDNA. We also analyzed somatic copy number alterations based on the targeted sequencing data using our in-house algorithm, and potentially targetable amplifications were detected. Assessment of mutations and copy number alterations in plasma cfDNA may provide a prognostic and diagnostic tool to assist decisions regarding optimal therapeutic strategies for PDAC patients.

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