Τίτλος:
Pik3ca mutational status in circulating tumor cells can change during disease recurrence or progression in patients with breast cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Molecular characterization of circulating tumor cells (CTC) is crucial for the investigation of molecular-targeted therapies while PIK3CA somatic mutations play a crucial role in therapy response. We investigated the presence of PIK3CA mutations in CTC and whether this is associated with clinical outcome.
We developed and validated an ultrasensitive methodology for the detection of PIK3CA mutations that is based on a combination of allele-specific, asymmetric rapid PCR and melting analysis. We analyzed PIK3CA hotspot mutations in: (i) a training group consisting of EpCAM-positive CTC fraction from 37 patients with clinically confirmed metastasis, and 26 healthy female volunteers and 15 primary breast tumor tissues and (ii) an independent group consisting of EpCAM-positive CTC fraction from 57 metastatic and 118 operable breast cancer patients and 76 corresponding primary tumors.
The assay could detect 0.05% of mutated dsDNA in the presence of 99.95% wtDNA for both exons (9 and 20) and was highly specific (0/26 healthy donors). PIK3CA mutations were identified in EpCAM-positive CTC in 20 of 57(35.1%) and in 23 of 118 (19.5%) patients with metastatic and operable breast cancer, and in 45 of 76(59.2%) corresponding FFPEs. Our data indicate that PIK3CA mutational status in CTCs can change during disease progression and is associated with worse survival (P ? 0.047).
PIK3CA hotspot mutations are present at a relatively high frequency in CTCs and their presence is associated with worse survival in patients with breast cancer with metastasis. Evaluation of PIK3CA mutational status in CTCs is a strategy with potential clinical application. Clin Cancer Res; 20(22); ©-2014 American Association for Cancer Research.
Συγγραφείς:
Markou, A.
Farkona, S.
Schiza, C.
Efstathiou, T.
Kounelis, S.
Malamos, N.
Georgoulias, V.
Lianidou, E.
Περιοδικό:
Clinical Cancer Research
Εκδότης:
American Association for Cancer Research Inc.
Λέξεις-κλειδιά:
cyclophosphamide; cytokeratin 19; docetaxel; double stranded DNA; epirubicin; epithelial cell adhesion molecule; messenger RNA; recombinant granulocyte colony stimulating factor; phosphatidylinositol 3 kinase; PIK3CA protein, human, Article; bone metastasis; brain metastasis; breast cancer; breast cancer cell line; cancer adjuvant therapy; cancer growth; cancer recurrence; circulating tumor cell; controlled study; early cancer; exon; gene expression; high resolution melting analysis; hotspot mutation; human; human cell; human tissue; liver metastasis; lung metastasis; major clinical study; multiple cycle treatment; mutational analysis; overall survival; PIK3CA gene; polymerase chain reaction; progression free survival; sensitivity and specificity; somatic mutation; Breast Neoplasms; cancer staging; case control study; disease course; female; genetics; metabolism; mortality; mutation; nucleotide sequence; pathology; procedures; prognosis; tumor cell line; tumor embolism; tumor recurrence, Breast Neoplasms; Case-Control Studies; Cell Line, Tumor; Disease Progression; DNA Mutational Analysis; Exons; Female; Humans; Mutation; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplastic Cells, Circulating; Phosphatidylinositol 3-Kinases; Prognosis; Sensitivity and Specificity
DOI:
10.1158/1078-0432.CCR-14-0149
