title: Number of somatic mutations in the mitochondrial D-loop region indicates poor prognosis in breast cancer, independent of TP53 mutation.
abstract: The objective of this study was to investigate whether somatic mutations in the mitochondrial DNA (mtDNA) D-loop region correlate with known prognostic factors, namely, age, tumor size, lymph node status, metastasis, tumor-node-metastasis stage, lymphovascular invasion, and status of the progesterone receptor, estrogen receptor, ERBB2 (alias HER2/neu), and TP53 proteins (as determined by immunohistochemistry) and to investigate their relationship, if any, to TP53 mutations in human breast cancer. Thirty breast tumors without BRCA mutation, along with adjacent nontumorous tissues, were genotyped for the mtDNA D-loop region and for the promoter as well as the coding region of the TP53 gene. Clinicopathological parameters were recorded and assessed. In all, 17 somatic mtDNA D-loop mutations were identified, in 13 of 30 tumor samples (43%); two mutations were novel: 544C>T and 16510A>C. Four TP53 mutations were found in six tumor samples (20%), and two (c.437G>A and c.706T>C) were novel. Only progesterone receptor status correlated with the number of somatic mtDNA D-loop mutations (likelihood chi-square test; P < 0.05). Somatic mutations in the mtDNA D-loop and in TP53 were independent of each other (Fisher's exact test; P > 0.05). These results suggest that the number of somatic mtDNA D-loop mutations may be an indicator of poor prognosis through a mechanism independent of TP53.
authors.affiliation: Department of Surgery, Changhua Christian Hospital, Taiwan.
authors.forename: Shou-Jen
authors.initials: SJ
authors.lastname: Kuo
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Gwo-Chin
authors.initials: GC
authors.lastname: Ma
authors.forename: Shou-Tung
authors.initials: ST
authors.lastname: Chen
authors.forename: Shun-Ping
authors.initials: SP
authors.lastname: Chang
authors.forename: Wen-Yin
authors.initials: WY
authors.lastname: Lin
authors.forename: Yen-Chieh
authors.initials: YC
authors.lastname: Chen
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Lee
authors.forename: Ta-Tsung
authors.initials: TT
authors.lastname: Lin
authors.forename: Chin-San
authors.initials: CS
authors.lastname: Liu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D016009:Chi-Square Distribution; D019175:DNA Methylation; D004252:DNA Mutational Analysis / Q000379:methods*; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53