期刊
GYNECOLOGIC ONCOLOGY
卷 104, 期 1, 页码 129-133出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2006.07.010
关键词
mitochondrial DNA; D-loop; ovarian cancer; mutations; polymorphisms
Objective. To date, most mtDNA mutations in cancer have been identified in the control region (D-loop) containing the major promoters. However, almost all studies used one sample per tumor and there is no clear evidence whether metastatic deposits harbor different mtDNA variants. To establish whether different mtDNA variants can be found in the same cancer but at different sites, we analyzed a series of unilateral and bilateral primary epithelial ovarian cancers as well as paired metastatic tumor deposits. Methods. We sequenced the D-loop region in 52 different tumor samples of 35 ovarian cancer cases, as well as matched normal tissues. Seventeen of those 35 cases had bilateral ovarian cancer, with a sample from each tumor analyzed. Results. Eighty-six polymorphisms (4 new in ovarian cancer) were detected, and 9 different somatic mtDNA mutations were found in 26% (9 of 35) of ovarian cancer cases; all were homoplasmic in nature. Six of the mutations were novel in ovarian cancer. In 24% (4 of 17) of cases with bilateral ovarian tumors, different mtDNA variants were found between paired tumors, suggesting the presence of different clonal populations of cancer cells. Metastatic tumor deposits showed identical mtDNA variants to those found in at least one of the ovarian tumors in cases with bilateral ovarian cancer. Conclusion. Our data demonstrate that multiple tumor samples from the same patient may harbor different mtDNA variants. (c) 2006 Elsevier Inc. All rights reserved.
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