TY - JOUR
TI - PIK3CA hotspot mutations in circulating tumor cells and paired circulating tumor DNA in breast cancer: a direct comparison study
AU - Tzanikou, E.
AU - Markou, A.
AU - Politaki, E.
AU - Koutsopoulos, A.
AU - Psyrri, A.
AU - Mavroudis, D.
AU - Georgoulias, V.
AU - Lianidou, E.
JO - Molecular Oncology
PY - 2019
VL - 13
TODO - 12
SP - 2515-2530
PB - John Wiley and Sons Ltd
SN - 1574-7891
TODO - 10.1002/1878-0261.12540
TODO - circulating tumor DNA;  epithelial cell adhesion molecule;  pik3ca protein;  tumor protein;  unclassified drug;  circulating tumor DNA;  phosphatidylinositol 4,5 bisphosphate 3 kinase;  PIK3CA protein, human, Article;  circulating tumor cell;  controlled study;  DNA isolation;  droplet digital polymerase chain reaction;  early cancer;  female;  gene amplification;  gene mutation;  human;  human cell;  human tissue;  major clinical study;  metastatic breast cancer;  primary tumor;  priority journal;  amino acid substitution;  blood;  breast tumor;  comparative study;  genetics;  MCF-7 cell line;  metabolism;  missense mutation;  pathology;  tumor embolism, Amino Acid Substitution;  Breast Neoplasms;  Circulating Tumor DNA;  Class I Phosphatidylinositol 3-Kinases;  Female;  Humans;  MCF-7 Cells;  Mutation, Missense;  Neoplastic Cells, Circulating
TODO - Liquid biopsy analysis, mainly based on circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), provides an extremely powerful tool for the molecular profiling of cancer patients in real time. In this study, we directly compared PIK3CA hotspot mutations (E545K, H1047R) in EpCAM-positive CTCs and paired plasma-ctDNA in breast cancer (BrCa). PIK3CA hotspot mutations in CTCs and ctDNA were analyzed using our previously developed highly sensitive (0.05%), specific, and validated assay in plasma-ctDNA from 77 early and 73 metastatic BrCa patients and 40 healthy donors. We further analyzed and directly compared PIK3CA hotspot mutations in DNAs isolated from CellSearch® cartridges (CTCs) and paired plasma-ctDNA, in 56 cases of early and 27 cases of metastatic breast cancer, and 16 corresponding primary tumors. In plasma-ctDNA, PIK3CA hotspot mutations were identified in 30/77(39.0%) early and 35/73(47.9%) metastatic BrCa cases; none (0/40, 0%) of the healthy donors’ plasma-ctDNA samples were positive. Our direct comparison study in DNAs isolated from CellSearch® cartridges (CTCs) and paired plasma-ctDNA from the same blood draws has shown a lack of concordance in early BrCa (27/56, 48.2%), while the concordance in the metastatic setting was higher (18/27, 66.6%). Our results were validated by ddPCR methodology, and the concordance between our assay and ddPCR for PIK3CA E545K hotspot mutation was 30/37 (81.1%). In many cases, PIK3CA hotspot mutations were detected in samples found to be negative for CTCs in CellSearch®. Our data demonstrated for the first time that (a) PIK3CA hotspot mutations are present at high frequencies in CTCs isolated from CellSearch® cartridges and paired plasma-ctDNA both in early and metastatic BrCa, (b) the detection and concordance of PIK3CA hotspot mutations between plasma-ctDNA and CTCs are higher in the metastatic setting, (c) PIK3CA mutational status significantly changes after therapeutic intervention, and (d) PIK3CA mutation detection in CTCs and plasma-ctDNA provides complementary information. © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
ER -