Microarray comparative genomic hybridization reveals genome-wide patterns of DNA gains and losses in post-Chernobyl thyroid cancer

被引:24
作者
Kimmel, Robert R.
Zhao, Lue Ping
Nguyen, Doan
Lee, Somnit
Aronszajn, Mark
Cheng, Chun
Troshin, Vladislav P.
Abrosimov, Alexander
Delrow, Jeffrey
Tuttle, R. Michael
Tsyb, Anatoli E.
Kopecky, Kenneth J.
Davis, Scott
Neiman, Paul E.
机构
[1] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA
[2] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA
[3] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA
[4] Inst Pathol, Bryansk, Russia
[5] Russian Acad Med Sci, Med Radiol Res Ctr, Obninsk, Russia
[6] Mem Sloan Kettering Canc Ctr, Div Endocrinol, New York, NY 10021 USA
[7] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA
[8] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA
关键词
D O I
10.1667/RR0547.1
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Genetic gains and losses resulting from DNA strand breakage by ionizing radiation have been demonstrated in vitro and suspected in radiation-associated thyroid cancer. We hypothesized that copy number deviations might be more prevalent, and/or occur in genomic patterns, in tumors associated with presumptive DNA strand breakage from radiation exposure than in their spontaneous counterparts. We used cDNA microarray-based comparative genome hybridization to obtain genome-wide, high-resolution copy number profiles at 14,573 genomic loci in 23 post-Chernobyl and 20 spontaneous thyroid cancers. The prevalence of DNA gains in tumors from cases in exposed individuals was two- to fourfold higher than for cases in unexposed individuals and up to 10-fold higher for the subset of recurrent gains. DNA losses for all cases were low and more prevalent in spontaneous cases. We identified unique patterns of copy variation (mostly gains) that depended on a history of radiation exposure. Exposed cases, especially the young, harbored more recurrent gains that covered more of the genome. The largest regions, spanning 1.2 to 4.9 Mbp, were located at 1p36.32-.33, 2p23.2-.3, 3p21.1-31, 6p22.1-.2, 7q36.1, 8q24.3, 9q34.11, 9q34.3, 11p15.5, 11q13.2-12.3, 14q32.33, 16p13.3, 16p11.2, 16q21-q12.2, 17q25.1, 19p13.31-qter, 22q11.21 and 22q13.2. Copy number changes, particularly gains, in post-Chernobyl thyroid cancer are influenced by radiation exposure and age at exposure, in addition to the neoplastic process. (c) 2006 by Radiation Research Society.
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收藏
页码:519 / 531
页数:13
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