PARP-1 Expression and <i>BRCA1</i> Mutations in Breast Cancer Patients’ CTCs

<i>BRCA1</i> and PARP are involved in DNA damage repair pathways. <i>BRCA1</i> mutations have been linked to higher likelihood of triple negative breast cancer (TNBC). The aim of the study was to determine PARP-1 expression and <i>BRCA1</i> mutations in circulatin...

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Bibliographic Details
Main Authors: Thodoris Sklias, Vasileios Vardas, Evangelia Pantazaka, Athina Christopoulou, Vassilis Georgoulias, Athanasios Kotsakis, Yiannis Vasilopoulos, Galatea Kallergi
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/14/7/1731
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Summary:<i>BRCA1</i> and PARP are involved in DNA damage repair pathways. <i>BRCA1</i> mutations have been linked to higher likelihood of triple negative breast cancer (TNBC). The aim of the study was to determine PARP-1 expression and <i>BRCA1</i> mutations in circulating tumor cells (CTCs) of BC patients. Fifty patients were enrolled: 23 luminal and 27 TNBC. PARP expression in CTCs was identified by immunofluorescence. Genotyping was performed by PCR-Sanger sequencing in the same samples. PARP-1 expression was higher in luminal (61%) and early BC (54%), compared to TNBC (41%) and metastatic (33%) patients. In addition, PARP-1 distribution was mostly cytoplasmic in luminal patients (<i>p</i> = 0.024), whereas it was mostly nuclear in TNBC patients. In cytokeratin (CK)-positive patients, those with the CK<sup>+</sup>PARP<sup>+</sup> phenotype had longer overall survival (OS, log-rank <i>p =</i> 0.046). Overall, nine mutations were detected; M1 and M2 were completely new and M4, M7 and M8 were characterized as pathogenic. M7 and M8 were predominantly found in metastatic TNBC patients (<i>p</i> = 0.014 and <i>p</i> = 0.002). Thus, PARP-1 expression and increased mutagenic burden in TNBC patients’ CTCs, could be used as an indicator to stratify patients regarding therapeutic approaches.
ISSN:2072-6694