WHOLE SEQUENCING OF THE MITOCHONDRIAL GENOME OF BREAST CANCER TISSUE IN MEXICAN-MESTIZO POSTMENOPAUSAL WOMEN WITH DIFFERENT BODY MASS INDEX.

REVISTA DE INVESTIGACION CLINICA-CLINICAL AND TRANSLATIONAL INVESTIGATION(2019)

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摘要
Background: Mitochondrial and oxidative stress has been related to obesity and breast cancer being this cancer more frequent and more aggressive in postmenopausal women with obesity. Objective: The objective of this study was to investigate whether Mexican-Mestizo postmenopausal women with breast cancer and obesity present different somatic mutations in the mitochondrial DNA (mtDNA) when compared to women with normal body mass index (BMI). Subjects and Methods: We included six Mexican-Mestizo postmenopausal women bearing breast cancer and who underwent mastectomy or breast-conserving surgery. BMI was determined in each case. Patients' genomic DNA was isolated from blood leukocytes and tumor tissue samples. Whole mtDNA sequence was determined by MitoChip v2.0 mitochondrial resequencing array, and data were analyzed using the GeneChip Sequence Analysis Software. Tumor mtDNA sequence was compared with matched leukocyte mtDNA sequence. Results: Three women had a normal BMI and three presented obesity. Overall, we found 64 genetic variants: 53.1% were somatic mutations and 46.9% were polymorphisms; 44.1% were in the non-coding region and 55.9% were in genes that encode for mitochondrial proteins. Among the somatic mutations, 67.7% were in patients with normal BMI and 32.3% in patients with obesity. Conclusions: We did not find a higher frequency of mitochondrial somatic mutations in postmenopausal women with breast cancer and obesity compared to those with normal BMI. However, results could be due to the small number of women studied.
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关键词
Breast cancer,Body mass index,Mexican-Mestizo postmenopausal women,Mitochondria genome,Somatic mutations
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