Mutation profiling of both cfDNAs and CTCs in gynecological cancer patients

Background: Cell-free circulating DNA (cfDNA) and circulating tumor cells (CTCs) are emerging minimally invasive cancer biomarkers that help with early diagnosis, prognosis and therapeutic target selection. Combined use of cfDNA and CTCs provides complementary information about tumor cell heterogeneity thus helping to identify genetic mutations relevant in clinical decision making. Patients and methods: cfDNA and CTCs were isolated from whole blood specimens of 20 gynecological cancer patients by CD-PRIME™. We performed targeted sequencing across 51 actionable genes in 20 cfDNA and ctcDNA, and then analyzed genetic mutations and clinical significance. Results: A total of 33 somatic variants were found in 16 actionable genes. A genetic variant analysis revealed 15 somatic variants in the cfDNA and 20 somatic variants in CTCs sample, only two variants were found in common. The most frequently altered genes in cfDNA samples were TP53 , PTCH1 , FGFR , and BRCA2 . in contrast, the most frequently altered genes in CTCs sample were TP53 , BRCA1 , TSC2 , ERBB2 and PTCH1 . An in silico analysis revealed that 60% of somatic variants (20 out of 33) were potentially pathogenic mutations as expected. Detected BRCA1 p.S573 frameshift mutation and BRCA2 p.Q1683 nonsense mutation lead to loss-of-function of BRCA1 and BRCA2 . Conclusion: Our study shows that the genetic profiling of cfDNA and CTCs together provides more enriched genomic information for guiding preclinical and clinical strategies and targeted therapies.