Genomic instability at the 13q31 locus and somatic mtDNA mutation in the D-loop site correlate with tumor aggressiveness in sporadic Brazilian breast cancer cases
Clinics
;
67(10): 1181-1190, Oct. 2012. ilus, tab
Article
in English
| LILACS
| ID: lil-653482
ABSTRACT
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.
Full text:
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Index:
LILACS (Americas)
Main subject:
Breast Neoplasms
/
DNA, Mitochondrial
/
Carcinoma
/
Genomic Instability
Type of study:
Etiology study
/
Incidence study
/
Observational study
/
Prognostic study
/
Risk factors
Limits:
Adult
/
Aged
/
Female
/
Humans
Country/Region as subject:
South America
/
Brazil
Language:
English
Journal:
Clinics
Journal subject:
Medicine
Year:
2012
Type:
Article
Affiliation country:
Brazil
Institution/Affiliation country:
FIOCRUZ/BR
/
Universidade do Estado do Rio de Janeiro/BR
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