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

Erina Takai, Yasushi Totoki, Hiromi Nakamura, Chigusa Morizane, Satoshi Nara, Natsuko Hama, Masami Suzuki, Eisaku Furukawa, Mamoru Kato, Hideyuki Hayashi, Takashi Kohno, Hideki Ueno, Kazuaki Shimada, Takuji Okusaka, Hitoshi Nakagama, Tatsuhiro Shibata, Shinichi Yachida

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number18425
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015 Dec 16
Externally publishedYes

Fingerprint

Pancreatic Neoplasms
DNA
Adenocarcinoma
Plasma Cells
Neoplasms
High-Throughput Nucleotide Sequencing
p16 Genes
Mutation
Gene Frequency
Genes
Genome
Polymerase Chain Reaction

ASJC Scopus subject areas

  • General

Cite this

Takai, E., Totoki, Y., Nakamura, H., Morizane, C., Nara, S., Hama, N., ... Yachida, S. (2015). Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer. Scientific reports, 5, [18425]. https://doi.org/10.1038/srep18425

Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer. / Takai, Erina; Totoki, Yasushi; Nakamura, Hiromi; Morizane, Chigusa; Nara, Satoshi; Hama, Natsuko; Suzuki, Masami; Furukawa, Eisaku; Kato, Mamoru; Hayashi, Hideyuki; Kohno, Takashi; Ueno, Hideki; Shimada, Kazuaki; Okusaka, Takuji; Nakagama, Hitoshi; Shibata, Tatsuhiro; Yachida, Shinichi.

In: Scientific reports, Vol. 5, 18425, 16.12.2015.

Research output: Contribution to journalArticle

Takai, E, Totoki, Y, Nakamura, H, Morizane, C, Nara, S, Hama, N, Suzuki, M, Furukawa, E, Kato, M, Hayashi, H, Kohno, T, Ueno, H, Shimada, K, Okusaka, T, Nakagama, H, Shibata, T & Yachida, S 2015, 'Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer', Scientific reports, vol. 5, 18425. https://doi.org/10.1038/srep18425
Takai, Erina ; Totoki, Yasushi ; Nakamura, Hiromi ; Morizane, Chigusa ; Nara, Satoshi ; Hama, Natsuko ; Suzuki, Masami ; Furukawa, Eisaku ; Kato, Mamoru ; Hayashi, Hideyuki ; Kohno, Takashi ; Ueno, Hideki ; Shimada, Kazuaki ; Okusaka, Takuji ; Nakagama, Hitoshi ; Shibata, Tatsuhiro ; Yachida, Shinichi. / Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer. In: Scientific reports. 2015 ; Vol. 5.
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