Utility of targeted deep sequencing for detecting circulating tumor DNA in pancreatic cancer patients.
Park, Joo Kyung
Kim, Yeon Jeong
Springer Science and Business Media LLC
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Park, G., Park, J. K., Son, D., Shin, S., Kim, Y. J., Jeon, H., Lee, J., et al. (2018). Utility of targeted deep sequencing for detecting circulating tumor DNA in pancreatic cancer patients.. Sci Rep, 8 (1), 11631. https://doi.org/10.1038/s41598-018-30100-w
Targeted deep sequencing across broad genomic regions has been used to detect circulating tumor DNA (ctDNA) in pancreatic ductal adenocarcinoma (PDAC) patients. However, since most PDACs harbor a mutation in KRAS, sequencing of broad regions needs to be systemically compared to analyzing only KRAS mutations for PDAC. Using capture-based targeted deep sequencing, we detected somatic tumor mutations in 17 fine needle aspiration biopsy and 69 longitudinal cell-free DNA (cfDNA) samples from 17 PDAC patients. KRAS mutations were detected in 10 out of 17 pretreatment patient plasma samples. Next, interrogation of genetic alterations in matched primary tumor samples detected ctDNA in 12 of 17 pretreatment plasma samples and cfDNA sequencing across the 83 target genes identified ctDNA in 15 of 17 cases (88.2% sensitivity). This improved sensitivity of ctDNA detection resulted in enhanced tumor burden monitoring when we analyzed longitudinal plasma samples. We found that cfDNA sequencing detected the lowest mutant allelic fractions and number of variants when complete response or partial response to chemotherapy was achieved. We demonstrated that ctDNA levels measured by targeted deep sequencing sensitively indicate the presence of cancer and correlate well with clinical responses to therapy and disease progression in PDAC patients.
Humans, Pancreatic Neoplasms, Biopsy, Fine-Needle, DNA Mutational Analysis, Mutation, Middle Aged, Female, Male, Proto-Oncogene Proteins p21(ras), High-Throughput Nucleotide Sequencing, Circulating Tumor DNA
External DOI: https://doi.org/10.1038/s41598-018-30100-w
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284736
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/