Taruna Rajagopal1, Arun Seshachalam2, Arunachalam Jothi3, Krishna Kumar Rathnam4, Srikanth Talluri5,6, Sivaramakrishnan Venkatabalasubranian7, Nageswara Rao Dunna8. 1. Cancer Genomics Laboratory, Department of Biotechnology, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, 613 401, India. 2. Department of Medical and Paediatric Oncology, Dr.G.V.N Cancer Institute, Singarathope, Trichy, 620 008, India. 3. Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, 613 401, India. 4. Department of Hemato Oncology - Medical Oncology and Bone Marrow Transplantation, Meenakshi Mission Hospital & Research Centre, Madurai, 625 107, India. 5. Dana Farber Cancer Institute, Boston, MA, 02215, USA. 6. Veterans Administration Boston Healthcare System, West Roxbury, MA, 02132, USA. 7. Department of Genetic Engineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur Campus, Chennai, Tamil Nadu, 603 203, India. 8. Cancer Genomics Laboratory, Department of Biotechnology, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, 613 401, India. dnrao@biotech.sastra.edu.
Abstract
BACKGROUND: The frequency of triple-negative breast cancer (TNBC) incidence varies among different populations suggesting the involvement of genetic components towards TNBC development. Previous studies have reported that BRCA1/2 germline mutations confer a lifetime risk of developing TNBC. However, there is hardly any information regarding the common pathogenic variants (PVs) in BRCA1/2 genes that contribute to TNBC in the Indian population. Hence, we screened for PVs in BRCA1/2 and their association with clinico-pathological features in TNBC patients. METHODS AND RESULTS: The study recruited 59 TNBC patients without hereditary breast and ovarian cancer (HBOC) from South India. The entire BRCA1 and BRCA2 genes were sequenced for the 59 patients using the Illumina HiSeq X Ten sequencer. Among the 59 TNBC genomic DNA samples sequenced, BRCA mutations were identified in 8 patients (13.6%), BRCA1 mutations in 6 patients, and BRCA2 mutations in 2 patients. Among the 6 BRCA1 mutations, three were c.68_69delAG (185delAG) mutation. Remarkably, all the TNBC patients with BRCA mutations exhibited higher-grade tumors (grade 2 or 3). However, among all the BRCA mutation carriers, only one patient with a BRCA2 mutation (p.Glu1879Lys) developed metastasis. CONCLUSION: Our data advocates that South Indian women with higher grade TNBC tumors and without HBOC could be considered for BRCA mutation screening, thereby enabling enhanced decision-making and preventive therapy.
BACKGROUND: The frequency of triple-negative breast cancer (TNBC) incidence varies among different populations suggesting the involvement of genetic components towards TNBC development. Previous studies have reported that BRCA1/2 germline mutations confer a lifetime risk of developing TNBC. However, there is hardly any information regarding the common pathogenic variants (PVs) in BRCA1/2 genes that contribute to TNBC in the Indian population. Hence, we screened for PVs in BRCA1/2 and their association with clinico-pathological features in TNBC patients. METHODS AND RESULTS: The study recruited 59 TNBC patients without hereditary breast and ovarian cancer (HBOC) from South India. The entire BRCA1 and BRCA2 genes were sequenced for the 59 patients using the Illumina HiSeq X Ten sequencer. Among the 59 TNBC genomic DNA samples sequenced, BRCA mutations were identified in 8 patients (13.6%), BRCA1 mutations in 6 patients, and BRCA2 mutations in 2 patients. Among the 6 BRCA1 mutations, three were c.68_69delAG (185delAG) mutation. Remarkably, all the TNBC patients with BRCA mutations exhibited higher-grade tumors (grade 2 or 3). However, among all the BRCA mutation carriers, only one patient with a BRCA2 mutation (p.Glu1879Lys) developed metastasis. CONCLUSION: Our data advocates that South Indian women with higher grade TNBC tumors and without HBOC could be considered for BRCA mutation screening, thereby enabling enhanced decision-making and preventive therapy.
Authors: Evelyn Jiagge; Aisha Souleiman Jibril; Dhananjay Chitale; Jessica M Bensenhaver; Baffour Awuah; Mark Hoenerhoff; Ernest Adjei; Mahteme Bekele; Engida Abebe; S David Nathanson; Kofi Gyan; Barbara Salem; Joseph Oppong; Francis Aitpillah; Ishmael Kyei; Ernest Osei Bonsu; Erica Proctor; Sofia D Merajver; Max Wicha; Azadeh Stark; Lisa A Newman Journal: Ann Surg Oncol Date: 2016-07-28 Impact factor: 5.344