ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/ERR136/051/ERR13613451/ERR13613451.fastq.gzprimaryOK200GenomicsAIMMSCRAmity Institute of Molecular Medicine & Stem Cell Researchhttps://www.ebi.ac.uk/ena/browser/view/PRJEB79498Background: Triple-negative breast cancers (TNBCs) are pathologically the most aggressive and heterogenous subtype of carcinoma breast displaying increased chemo-resistance and a high rate of relapse. A compelling need exists to discover specific gene mutation(s) and exomic mutational landscape associated with Indian TNBC patients in identifying potential therapeutic target(s) for effective treatment. Methods: The status of the hormone receptors and human epidermal growth factor receptor 2 was confirmed. Genomic DNA was extracted from TNBC tissues and adjacent non-cancerous breast tissues. Quantification and quality of gDNA samples were checked. Whole exome sequencing (WES) was performed on 15 TNBC patients along with 5 random adjacent non-cancerous tissue specimens. WES data alignment and mapping to reference human genome hg19 was done using BWA, SAMtools, and Picard tools. The data analysis and mutation calling were performed using the Genome Analysis Toolkit (GATK). The signal and PANTHER pathways tools were used for mutational significance and pathway analysis, respectively. Findings: Our data reveals that the TNBC genomes carried an average of ~106 mutations per sample. MutSig2CV analysis showed the most significant recurrent mutations in CTNNB1 (47% 7/15), TP53 (33% 5/15), SLC7A8 (27% 4/15), AMOT (20% 3/15), CLEC11A (20% 3/15), and ECHDC1 (13% 2/15) with a q value of ≤ 0.1. We also observed recurrent mutations in other important cancer-associated genes such as ABCC3, BRCA1, BRCA2, BIRC6, CDH7, CSMD3, MUC12, MUC16, NT5C1B,PIK3CA, POLE, STK31, TTN, and ZFHX4. Interestingly, the TNBC genomes exhibited a predominance of signature 1 associated with spontaneous deamination of 5-methylcytosine, signature 3 represented the failure of DNA double-strand break repair by homologous recombination, while signature 5 correlated with transcriptional strand bias. Furthermore, these mutations were involved in several major signaling pathways such as the Wnt, p53, PDGF, cadherin, DNA replication, integrin, and apoptosis signaling. Interpretation: Together, the findings of this study indicated that a crucial role played by these key exonic mutations in Indian TNBC patients which could be utilized in screening and TNBC risk predictions in clinical settings, and developing potential targeted therapeutics for TNBC. Furthermore, studies may focus on identifying genetic variability among TNBC patients for developing effective treatment.ENAtriple-receptor negative breast cancer, Scientific Bias, Materials, Complete Exome, Breast Neoplasms, Ecological Fallacy, Neoplasms, p53, Truncation, Benign Neoplasm, Triple-Negative Breast Cancers, Gene, Systematic Bias, Tumor, PRO2286, LFS1, Malignant, TNBC, Tp53, dIKK-gamma, Mutations, triple-negative breast cancer, Relative, Mesc, triple-negative breast carcinoma, bbl, Core Genome, deamination, DmIKK-gamma, Epidemiologic Biase, Asian Indian, DNA Damage Response, symptoms, Mass, Screening, Whole Transcriptome, Transcriptome Sequencing, Ecological, dmIKKgamma, Catnb, ctnnb, IKK[[gamma]], IKKg, KEY, Key, Fallacies, average, treatment, study, Ecological Biases, WES, Complete, ctnnb1, Exome Sequencings, Genetic, Triple Negative Breast Cancer, BCC7, Malignancy, Genomes, Complete Exome Sequencing, Breast Cancers, Whole Transcriptome Sequencing, Accessory Genome, Aggregation, Sequencing, genetic, Neoplasias, Whole Exome, Trp53, OK/SW-cl.35, IKK, malignant neoplasm, Statistical Biases, Clients, Whole, Triple Negative Breast Neoplasm, sample, Therapies, Ecological Bias, Malignancies, Systematic, TRP53, Epidemiologic Biases, constitutitional genetic, Bfc, single organism signaling, Cancer, Tumors, Biase, Therapy, Fallacy, screening, findings, Complete Exome Sequencings, Malignant Neoplasm, Scientific, Asian Indians, Epidemiologic, Exome, familial, Triple-Negative Breast Cancer, Truncation Biases, Hindu, armadillo, Ecological Fallacies, Cistrons, Client, Pangenome, Xp53, beta-catenin, Outcome Measurement Errors, IKKgamma, Exome Sequencing, DmIKKgamma, disease management., CTNNB, Experimental, MT, Benign, Screenings, dIKK, Mass Screenings, Relative Risks, Kenny, Neoplasm, Errors, Triple-Negative, Genetic Materials, bfy, Truncation Bias, Genetic Material, Relative Risk, Complete Transcriptome, MRD19, Triple-Negative Breast Neoplasms, Breast Neoplasm, primary cancer, Bias, Complete Transcriptome Sequencing, Indian Asian, ER Negative PR Negative HER2 Negative Breast Cancer, Risk, ER-Negative PR-Negative HER2-Negative Breast Neoplasms, Dmikkgamma, Risks, IKK-gamma, Biases, signs, Benign Neoplasms, Deaminations, Cancers, Outcome Measurement, CG16910, malignant tumor, Treatments, sample population, Malignant Neoplasms, Experimental Bias, ER Negative PR Negative HER2 Negative Breast Neoplasms, Outcome Measurement Error, Pan-genome, DmelCG16910, signalling process, Patient, Error, Therapeutic, Material, Aggregation Bias, Breast Cancer, Triple-Negative Breast Neoplasm, Statistical Bias, Whole Exome Sequencing, P53, p44, bhy, Cistron, Treatment, inherited genetic, Statistical, Indian, Transcriptome Sequencings, hereditary, ER-Negative PR-Negative HER2-Negative Breast Cancer, Neoplasiatriple-receptor negative breast cancer, Materials, Complete Exome Sequencings, Complete Exome, Breast Neoplasms, Asian Indians, Exome, Triple-Negative Breast Cancer, Triple-Negative Breast Cancers, Gene, Hindu, Cistrons, TNBC, Mutations, triple-negative breast cancer, Exome Sequencing, Client., triple-negative breast carcinoma, Asian Indian, Genetic Materials, Triple-Negative, Whole Transcriptome, Transcriptome Sequencing, Genetic Material, WES, Complete Transcriptome, Triple-Negative Breast Neoplasms, Breast Neoplasm, Complete, Complete Transcriptome Sequencing, Exome Sequencings, Genetic, Indian Asian, ER Negative PR Negative HER2 Negative Breast Cancer, Triple Negative Breast Cancer, ER-Negative PR-Negative HER2-Negative Breast Neoplasms, Complete Exome Sequencing, Breast Cancers, Whole Transcriptome Sequencing, INSDC_feature:gene, Sequencing, ER Negative PR Negative HER2 Negative Breast Neoplasms, Whole Exome, Patient, Material, Clients, Whole, Triple Negative Breast Neoplasm, Breast Cancer, Triple-Negative Breast Neoplasm, Whole Exome Sequencing, Cistron, Indian, Transcriptome Sequencings, ER-Negative PR-Negative HER2-Negative Breast CancerfalseWhole exome sequencing for indentification of specific gene mutations in an Indian cohort of triple-negative breast cancer patientsThis study analyzed whole exome sequencing data from 15 Indian triple-negative breast cancer (TNBC) patients. On average, 106 mutations per sample were identified. The most significant recurrent mutations were found in genes including CTNNB1, TP53, and SLC7A8. Other cancer-associated genes also showed mutations. The TNBC genomes exhibited predominant mutational signatures related to spontaneous deamination, DNA repair failure, and transcriptional strand bias. These mutations were involved in several major signaling pathways. The findings highlight key exonic mutations in Indian TNBC patients that could be used for screening, risk prediction, and developing targeted therapeutics. Further studies on genetic variability among TNBC patients are suggested for improved treatment strategies.2024-08-292024-08-29PRJEB79498