High frequency of mitochondrial DNA D-loop mutations in Ewing's sarcoma

被引:11
作者
Yu, Man [1 ,2 ]
Wan, Yanfang [3 ]
Zou, Qinghua [4 ]
Xi, Yanwei
机构
[1] Univ Ottawa, Dept Biol, CAREG, Ottawa, ON K1N 6N5, Canada
[2] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada
[3] Tianjin Med Univ, Canc Hosp & Inst, Dept Biochem & Mol Biol, Tianjin 300060, Peoples R China
[4] China Natl Petr Corp, Cent Hosp, Dept Surg Oncol, Langfang 065000, Hebei Province, Peoples R China
关键词
Mitochondrial DNA; D-loop; Mutation; Ewing's sarcoma; BREAST-CANCER RISK; COPY NUMBER; OXIDATIVE STRESS; TUMORS; TUMORIGENESIS; OSTEOSARCOMA; POLYMORPHISM; FAMILY; DAMAGE; CELLS;
D O I
10.1016/j.bbrc.2009.09.085
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Somatic mutations and polymorphisms in the noncoding displacement (D)-loop of mitochondrial DNA (mtDNA) are present in a variety of human cancers. To investigate whether Ewing's sarcoma (EWS) harbors genetic alterations within the D-loop region and their potential association with EWS carcinogenesis, we analyzed and compared the complete mtDNA D-loop sequences from 17 pairs of tumor tissues and corresponding peripheral blood samples using the direct DNA sequencing method. Our results revealed that 12 of the 17 EWS tumor specimens (70.6%) carried 19 somatic mutations in the D-loop of mtDNA, including 11 single-base substitutions, 3 insertions and 5 deletions. Among the tested 17 patients, we screened a total of 40 germline polymorphisms including one novel sequence variant in the D-loop fragment. Most of these identified mutations and germline variations were clustered within two hypervariable segments (HVS1 and HVS2) as well as the homopolymeric C stretch between nucleotide position 303 and 309. In addition, there was no significant correlation between mtDNA D-loop mutations and various clinicopathological factors of EWS. In conclusion, our study reports for the first time that mtDNA D-loop mutations occur at a high frequency in EWS. These data provide evidence of mtDNA alterations' possible involvement in the initiation and/or progression of this rare malignancy. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:447 / 450
页数:4
相关论文
共 28 条
  • [1] What is a 'novel' mtDNA mutation - and does 'novelty' really matter?
    Bandelt, Hans-Juergen
    Salas, Antonio
    Bravi, Claudio M.
    [J]. JOURNAL OF HUMAN GENETICS, 2006, 51 (12) : 1073 - 1082
  • [2] MITOCHONDRIAL MUTATIONS MAY INCREASE OXIDATIVE STRESS - IMPLICATIONS FOR CARCINOGENESIS AND AGING
    BANDY, B
    DAVISON, AJ
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 1990, 8 (06) : 523 - 539
  • [3] The organization and inheritance of the mitochondrial genome
    Chen, XJ
    Butow, RA
    [J]. NATURE REVIEWS GENETICS, 2005, 6 (11) : 815 - 825
  • [4] Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease: is there a common mechanism?
    Chinnery, PF
    Samuels, DC
    Elson, J
    Turnbull, DM
    [J]. LANCET, 2002, 360 (9342) : 1323 - 1325
  • [5] Clayton D A, 2000, Hum Reprod, V15 Suppl 2, P11
  • [6] Mitochondrial DNA variant interactions modify breast cancer risk
    Covarrubias, Daniel
    Bai, Ren-Kui
    Wong, Lee-Jun C.
    Leal, Suzanne M.
    [J]. JOURNAL OF HUMAN GENETICS, 2008, 53 (10) : 924 - 928
  • [7] THE EWING FAMILY OF TUMORS - A SUBGROUP OF SMALL-ROUND-CELL TUMORS DEFINED BY SPECIFIC CHIMERIC TRANSCRIPTS
    DELATTRE, O
    ZUCMAN, J
    MELOT, T
    GARAU, XS
    ZUCKER, JM
    LENOIR, GM
    AMBROS, PF
    SHEER, D
    TURCCAREL, C
    TRICHE, TJ
    AURIAS, A
    THOMAS, G
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1994, 331 (05) : 294 - 299
  • [8] Mitochondrial DNA mutations in the D-loop region may not be frequent in cervical cancer: a discussion on pitfalls in mitochondrial DNA studies
    Fang, Hezhi
    Lu, Jianxin
    Wei, Jia
    Shen, Li-Jun
    Ding, Zhinan
    Li, Hongzhi
    Bai, Yidong
    [J]. JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2009, 135 (04) : 649 - 651
  • [9] EWS-FLI1 and EWS-ERG gene fusions are associated with similar clinical phenotypes in Ewing's sarcoma
    Ginsberg, JP
    de Alava, E
    Ladanyi, M
    Wexler, LH
    Kovar, H
    Paulussen, M
    Zoubek, A
    Dockhorn-Dworniczak, B
    Juergens, H
    Wunder, JS
    Andrulis, IL
    Malik, R
    Sorensen, PHB
    Womer, RB
    Barr, FG
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (06) : 1809 - 1814
  • [10] The mitochondrial DNA polymerase as a target of oxidative damage
    Graziewicz, MA
    Day, BJ
    Copeland, WC
    [J]. NUCLEIC ACIDS RESEARCH, 2002, 30 (13) : 2817 - 2824