Liquid biopsy-based comprehensive gene mutation profiling for gynecological cancer using CAncer Personalized Profiling by deep Sequencing

• Published in: Scientific reports Vol. 9; no. 1; pp. 10426 - 8
• Main Authors: Iwahashi, Naoyuki, Sakai, Kazuko, Noguchi, Tomoko, Yahata, Tamaki, Matsukawa, Hitomi, Toujima, Saori, Nishio, Kazuto, Ino, Kazuhiko
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.07.2019; Nature Publishing Group
• Subjects: 38/22; 38/23; 38/39; 38/77; 631/67/1517/1371; 631/67/1517/1709; 631/67/1517/1931; Adenomatous polyposis coli; Biomarkers, Tumor - genetics; Biopsy; BRCA1 protein; Cancer; Chemotherapy; Circulating Tumor DNA - genetics; DNA sequencing; DNA, Neoplasm - genetics; Epidermal growth factor receptors; Female; Genital Neoplasms, Female - genetics; Genital Neoplasms, Female - pathology; Genotyping; Gynecological cancer; Gynecology; High-Throughput Nucleotide Sequencing - methods; Humanities and Social Sciences; Humans; Liquid Biopsy - methods; MET protein; multidisciplinary; Mutation; Mutation - genetics; Neoplastic Cells, Circulating - pathology; Next-generation sequencing; Ovarian cancer; p53 Protein; Point mutation; Science; Science (multidisciplinary); Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-47030-w

Liquid biopsies of circulating tumor DNA (ctDNA) have recently been used as a non-invasive diagnostic tool for detecting tumor-specific mutations. We present a study of ctDNA liquid biopsies in gynecological cancer using an ultrasensitive next-generation sequencing-based method for ctDNA detection named CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). We performed CAPP-Seq with plasma-ctDNA obtained from 16 patients with gynecological cancer. In all cases, at least one non-synonymous somatic mutation was detected in the ctDNA. In the pre-treatment ctDNA, 4 of 16, 4/16, 5/16, 2/16, 2/16, and 2/16 patients had TP53 , KRAS , APC , PIK3CA , BRCA1 , and EGFR mutations, respectively. MET gene copy-number gains were detected in the ctDNA of 2 of 16 patients, and FISH analysis of the paired tumor samples confirmed these results. In 2 neoadjuvant chemotherapy-treated ovarian cancer patients, the changes in gene mutation patterns were associated with the treatment response. These findings suggest that CAPP-Seq-based liquid biopsies can be used for the genetic characterization of independent gynecological cancers with high frequency, and might be clinically useful for non-invasive tumor genotyping and therapeutic response monitoring.