Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer. - PubMed - NCBI
Sci Rep. 2015 Dec 16;5:18425. doi: 10.1038/srep18425.
Clinical utility of circulating tumor DNA for molecular assessment in pancreatic cancer.
Takai E1,
Totoki Y1,
Nakamura H1,
Morizane C2,
Nara S3,
Hama N1,
Suzuki M1,
Furukawa E4,
Kato M4,
Hayashi H2,5,
Kohno T5,
Ueno H2,
Shimada K3,
Okusaka T2,
Nakagama H6,
Shibata T1,7,
Yachida S1.
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.
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