Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer

Ling Ming Tseng, Pen H. Yin, Chin W. Chi, Chih Y. Hsu, Chew W. Wu, Liang Ming Lee, Yau Huei Wei, Hsin Chen Lee

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

Somatic mutations in mitochondrial DNA (mtDNA) have been demonstrated in various tumors, including breast cancer. However, it still remains unclear whether the alterations in mtDNA are related to the clinicopathological features and/or the prognosis in the breast cancer. We analyzed somatic mutations in the D-loop region, the common 4,977-bp deletion, and the copy number of mtDNA in breast cancer and paired nontumorous breast tissues from 60 Taiwanese patients. We found that 18 of the 60 (30%) breast cancers displayed somatic mutations in mtDNA D-loop region. The incidence of the 4,977-bp deletion in nontumorous breast tissues (47%) was much higher than that in breast cancers (5%). The copy number of mtDNA was significantly decreased in 38 of the 60 (63%) breast cancers as compared to their corresponding nontumorous breast tissues (P = 0.0008). The occurrence of D-loop mutations was associated with an older onset age (≥50 years old, P = 0.042), and tumors that lacked expressions of estrogen receptor and progesterone receptor (P = 0.024). Patients with mtDNA D-loop mutation and breast cancer had significantly poorer disease-free survival than those without mutation, when assessed by Kaplan-Meier curves and log-rank test (P = 0.005). Multivariate Cox regression analysis indicated that a D-loop mutation is a significant marker that is independent of other clinical variables and that it can be used to assess the prognosis of patients. Our findings suggest that somatic mutations in mtDNA D-loop can be used as a new molecular prognostic indicator in breast cancer.

Original languageEnglish
Pages (from-to)629-638
Number of pages10
JournalGenes Chromosomes and Cancer
Volume45
Issue number7
DOIs
Publication statusPublished - Jul 2006

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Mitochondrial DNA
Breast Neoplasms
Mutation
Breast
Progesterone Receptors
Age of Onset
Estrogen Receptors
Disease-Free Survival
Neoplasms
Regression Analysis
Incidence

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Tseng, L. M., Yin, P. H., Chi, C. W., Hsu, C. Y., Wu, C. W., Lee, L. M., ... Lee, H. C. (2006). Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer. Genes Chromosomes and Cancer, 45(7), 629-638. https://doi.org/10.1002/gcc.20326

Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer. / Tseng, Ling Ming; Yin, Pen H.; Chi, Chin W.; Hsu, Chih Y.; Wu, Chew W.; Lee, Liang Ming; Wei, Yau Huei; Lee, Hsin Chen.

In: Genes Chromosomes and Cancer, Vol. 45, No. 7, 07.2006, p. 629-638.

Research output: Contribution to journalArticle

Tseng, LM, Yin, PH, Chi, CW, Hsu, CY, Wu, CW, Lee, LM, Wei, YH & Lee, HC 2006, 'Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer', Genes Chromosomes and Cancer, vol. 45, no. 7, pp. 629-638. https://doi.org/10.1002/gcc.20326
Tseng, Ling Ming ; Yin, Pen H. ; Chi, Chin W. ; Hsu, Chih Y. ; Wu, Chew W. ; Lee, Liang Ming ; Wei, Yau Huei ; Lee, Hsin Chen. / Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer. In: Genes Chromosomes and Cancer. 2006 ; Vol. 45, No. 7. pp. 629-638.
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