Laura-Ancuta Pop1, Roxana-Maria Cojocneanu-Petric2, Valentina Pileczki2, Gabriela Morar-Bolba3, Alexandru Irimie4, Vladimir Lazar5, Claudio Lombardo6, Angelo Paradiso7, Ioana Berindan-Neagoe8. 1. Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania; Department of Functional Genomics and Experimental Pathology, The Oncology Institute "Prof. Dr. I Chiricuta", Cluj-Napoca, Cluj, Romania. 2. Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania. 3. Department of Radiotherapy, The Oncology Institute "Prof. Dr. Ion Chiricuţa", Cluj-Napoca, Romania; Department of Analytical Chemistry and Instrumental Analysis, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. 4. Department of Surgical Oncology and Gynecological Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; MEDFUTURE Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; Department of Surgical Oncology I, The Oncology Institute "Prof. Dr. Ion Chiricuţa", Cluj-Napoca, Romania. 5. Worldwide Innovative Network for Personalized Cancer Therapy, Villejuif, France. 6. Organization of European Cancer Institute, Brussels, Belgium. 7. Laboratorio Oncologia Sperimentale Clinica, Istituto Oncologico-Bari, Italy. Electronic address: a.paradiso@oncologico.bari.it. 8. Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania; Department of Functional Genomics and Experimental Pathology, The Oncology Institute "Prof. Dr. I Chiricuta", Cluj-Napoca, Cluj, Romania; MEDFUTURE Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. Electronic address: ioana.neagoe@umfcluj.ro.
Abstract
BACKGROUND: Recent studies have aimed to identify gene mutation profiles to explain the cause of TNBC therapy limitations. METHODS: The purpose of our study was to use Next Generation Sequencing (NGS) of 46 genes with a well-defined role in cancer in a cohort of TNBC patients in order to identify novel markers that could lead to the development of strategic, adjuvant, gene-targeted therapies. RESULTS: A total of 118 gene mutations in 35 genes, 75 mutations in BRCA1 and 92 mutations in BRCA2 were identified. The clinical assessment of the identified mutations showed 27 to be possibly damaging and 59 to be damaging. TP53, KDR, PIK3CA (rs3729687), ATM, AKT1 and KIT were among the most frequently mutated genes in our TNBC cohort. The SNP AKT1 (rs3730358) was suggested to modify the risk of breast cancer. SNP PIK3CA (rs3729687) is a damaging mutation that we found to be correlated with the prognosis of TNBC. The survival curve analysis showed that the presence of AKT1, TP53, KDR, KIT, BRCA1 and BRCA2 mutations is correlated with a poor prognosis. CONCLUSION: We show a strong association between TNBC and mutations in BRCA1/2 genes and the poor outcome of these patients. Moreover, we identified several other unknown mutations putatively associated with the poor prognosis of TNBC tumors. We also discovered novel mutations never before associated with breast cancer that could putatively account for the poor prognosis of the TNBC tumors.
BACKGROUND: Recent studies have aimed to identify gene mutation profiles to explain the cause of TNBC therapy limitations. METHODS: The purpose of our study was to use Next Generation Sequencing (NGS) of 46 genes with a well-defined role in cancer in a cohort of TNBC patients in order to identify novel markers that could lead to the development of strategic, adjuvant, gene-targeted therapies. RESULTS: A total of 118 gene mutations in 35 genes, 75 mutations in BRCA1 and 92 mutations in BRCA2 were identified. The clinical assessment of the identified mutations showed 27 to be possibly damaging and 59 to be damaging. TP53, KDR, PIK3CA (rs3729687), ATM, AKT1 and KIT were among the most frequently mutated genes in our TNBC cohort. The SNP AKT1 (rs3730358) was suggested to modify the risk of breast cancer. SNP PIK3CA (rs3729687) is a damaging mutation that we found to be correlated with the prognosis of TNBC. The survival curve analysis showed that the presence of AKT1, TP53, KDR, KIT, BRCA1 and BRCA2 mutations is correlated with a poor prognosis. CONCLUSION: We show a strong association between TNBC and mutations in BRCA1/2 genes and the poor outcome of these patients. Moreover, we identified several other unknown mutations putatively associated with the poor prognosis of TNBC tumors. We also discovered novel mutations never before associated with breast cancer that could putatively account for the poor prognosis of the TNBC tumors.
Authors: Daiana Cosmina Temian; Laura Ancuta Pop; Alexandra Iulia Irimie; Ioana Berindan-Neagoe Journal: J Breast Cancer Date: 2018-09-20 Impact factor: 3.588