Genomic instability at 13q31 locus and somatic mtDNA mutation in D-loop site correlate with tumor aggressiveness in sporadic Brazilian breast cancer cases
| Autor: | Carla Cristina Moreira, Franklin David Rumjanek, Humberto de Vitto, Andréa Carla de Souza Góoes, Elizabeth Avvad, Gilson Costa dos Santos-Jr, Claudia Vitoria de Moura Gallo |
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| Přispěvatelé: | Gilson Costa dos Santos, J, de Souza Góes, A, De Vitto, H, Moreira, C, Avvad, E, Rumjanek, F, de Moura GalloI, C |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Genome instability Mitochondrial DNA Somatic cell Loss of Heterozygosity Breast Neoplasms Locus (genetics) Biology Allelic Imbalance DNA Mitochondrial Genomic Instability Somatic mtDNA Mutation Cohort Studies Loss of heterozygosity Age Distribution Breast cancer Breast Cancer Biomarkers Tumor medicine Humans LOH Genotyping Aged Genetics lcsh:R5-920 Chromosomes Human Pair 13 Carcinoma General Medicine Clinical Science Middle Aged Genes p53 medicine.disease Molecular biology BIO/10 - BIOCHIMICA STRs Genetic Loci Microsatellite Female Neoplasm Grading lcsh:Medicine (General) Brazil Microsatellite Repeats |
| Zdroj: | Clinics, Volume: 67, Issue: 10, Pages: 1181-1190, Published: OCT 2012 Clinics, Vol 67, Iss 10, Pp 1181-1190 (2012) Clinics Clinics; v. 67 n. 10 (2012); 1181-1190 Clinics; Vol. 67 Núm. 10 (2012); 1181-1190 Clinics; Vol. 67 No. 10 (2012); 1181-1190 Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1980-5322 1807-5932 |
| Popis: | OBJECTIVE: Genomic instability is a hallmark of malignant tissues. In this work, we aimed to characterize nuclear and mitochondrial instabilities by determining short tandem repeats and somatic mitochondrial mutations, respectively, in a cohort of Brazilian sporadic breast cancer cases. Furthermore, we performed an association analysis of the molecular findings and the clinical pathological data. METHODS: We analyzed 64 matched pairs of breast cancer and adjacent non-cancerous breast samples by genotyping 13 nuclear short tandem repeat loci (namely, D2S123, TPOX, D3S1358, D3S1611, FGA, D7S820, TH01, D13S317, D13S790, D16S539, D17S796, intron 12 BRCA1 and intron 1 TP53) that were amplified with the fluorescent AmpFlSTR Identifiler Genotyping system (Applied Biosystems, USA) and by silver nitrate staining following 6% denaturing polyacrylamide gel electrophoresis. Somatic mtDNA mutations in the D-loop site were assessed with direct sequencing of the hypervariable HVI and HVII mitochondrial regions. RESULTS: Half of the cancer tissues presented some nuclear instability. Interestingly, the D13S790 locus was the most frequently affected (36%), while the D2S123 locus presented no alterations. Forty-two percent of the cases showed somatic mitochondrial mutations, the majority at region 303-315 poly-C. We identified associations between Elston grade III, instabilities at 13q31 region (p = 0.0264) and mtDNA mutations (p = 0.0041). Furthermore, instabilities at 13q31 region were also associated with TP53 mutations in the invasive ductal carcinoma cases (p = 0.0207). CONCLUSION: Instabilities at 13q31 region and the presence of somatic mtDNA mutations in a D-loop site correlated with tumor aggressiveness. |
| Databáze: | OpenAIRE |
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