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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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/7/1731 |
| _version_ | 1797440149728002048 |
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| author | Thodoris Sklias Vasileios Vardas Evangelia Pantazaka Athina Christopoulou Vassilis Georgoulias Athanasios Kotsakis Yiannis Vasilopoulos Galatea Kallergi |
| author_facet | Thodoris Sklias Vasileios Vardas Evangelia Pantazaka Athina Christopoulou Vassilis Georgoulias Athanasios Kotsakis Yiannis Vasilopoulos Galatea Kallergi |
| author_sort | Thodoris Sklias |
| collection | DOAJ |
| description | <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. |
| first_indexed | 2024-03-09T12:02:56Z |
| format | Article |
| id | doaj.art-a69883827cfa4d83a367d6b1ccab0719 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T12:02:56Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a69883827cfa4d83a367d6b1ccab07192023-11-30T23:01:16ZengMDPI AGCancers2072-66942022-03-01147173110.3390/cancers14071731PARP-1 Expression and <i>BRCA1</i> Mutations in Breast Cancer Patients’ CTCsThodoris Sklias0Vasileios Vardas1Evangelia Pantazaka2Athina Christopoulou3Vassilis Georgoulias4Athanasios Kotsakis5Yiannis Vasilopoulos6Galatea Kallergi7Laboratory of Genetics, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, GreeceLaboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, GreeceLaboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, GreeceOncology Unit, ST Andrews General Hospital of Patras, 26332 Patras, GreeceHellenic Oncology Research Group (HORG), 11526 Athens, GreeceDepartment of Medical Oncology, University General Hospital of Larisa, 41334 Larisa, GreeceLaboratory of Genetics, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, GreeceLaboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece<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.https://www.mdpi.com/2072-6694/14/7/1731PARP-1<i>BRCA1</i>circulating tumor cellsbreast cancertriple negative breast cancerluminal |
| spellingShingle | Thodoris Sklias Vasileios Vardas Evangelia Pantazaka Athina Christopoulou Vassilis Georgoulias Athanasios Kotsakis Yiannis Vasilopoulos Galatea Kallergi PARP-1 Expression and <i>BRCA1</i> Mutations in Breast Cancer Patients’ CTCs Cancers PARP-1 <i>BRCA1</i> circulating tumor cells breast cancer triple negative breast cancer luminal |
| title | PARP-1 Expression and <i>BRCA1</i> Mutations in Breast Cancer Patients’ CTCs |
| title_full | PARP-1 Expression and <i>BRCA1</i> Mutations in Breast Cancer Patients’ CTCs |
| title_fullStr | PARP-1 Expression and <i>BRCA1</i> Mutations in Breast Cancer Patients’ CTCs |
| title_full_unstemmed | PARP-1 Expression and <i>BRCA1</i> Mutations in Breast Cancer Patients’ CTCs |
| title_short | PARP-1 Expression and <i>BRCA1</i> Mutations in Breast Cancer Patients’ CTCs |
| title_sort | parp 1 expression and i brca1 i mutations in breast cancer patients ctcs |
| topic | PARP-1 <i>BRCA1</i> circulating tumor cells breast cancer triple negative breast cancer luminal |
| url | https://www.mdpi.com/2072-6694/14/7/1731 |
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