Since surgical resection of localized pancreatic cancer improves overall survival, its early detection would have substantial benefits. Circulating tumor DNA, which is drawing attention as a part of liquid biopsy, might be useful for pancreatic cancer detection. Although KRAS mutations appear in the majority of pancreatic cancer cases, screening for other gene mutations in plasma may improve detection.
We used the non-overlapping integrated read sequencing system (NOIR-SS), a next-generation sequencing method with improved accuracy, to sequence a panel of pancreatic cancer-related genes including KRAS, TP53, SMAD4, CTNNB1, CDKN2A, GNAS, HRAS, and NRAS (comprising 2.8 kb of genomic DNA) in plasma DNA. NOIR-SS eliminates PCR/sequencing errors by building a consensus sequence from reads with the same molecular barcode.
Of 77 patients with localized pancreatic cancer, 9 (11.7%) and 16 (20.8%) patients were variant-positive for KRAS and any of the aforementioned genes. Of 67 patients with metastatic pancreatic cancer, 28 (52.2%) and 35 (41.8%) patients were variant-positive for KRAS and any of the aforementioned genes. No variant was detected in 12 healthy individuals. Of 20 patients with intra-ductal papillary mucous neoplasms (IPMN), only one mutation in TP53 was found.
The sequencing system removed artifacts during the assay process, and achieved near complete elimination of variant detection in control populations, namely in healthy individuals and IPMN. Sequencing of pancreatic cancer-related genes revealed an approximately 10% increase in detection rate from that with KRAS alone, thus demonstrating the merit of analyzing multiple genes.
Osaka International Cancer Institute
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K. Kato: Employment (part time): DNA Chip Research Inc. All other authors have declared no conflicts of interest.