Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer.
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 (>or=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.
Department of Surgery, Taipei Veterans General Hospital, and National Yang-Ming University, Taiwan, Republic of China.
Ling-Ming
LM
Tseng
Pen-Hui
PH
Yin
Chin-Wen
CW
Chi
Chih-Yi
CY
Hsu
Chew-Wun
CW
Wu
Liang-Ming
LM
Lee
Yau-Huei
YH
Wei
Hsin-Chen
HC
Lee
D000367:Age Factors; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D017384:Sequence Deletion
D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm