Microarray comparative genomic hybridization reveals genome-wide patterns of DNA gains and losses in post-Chernobyl thyroid cancer.
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.
Kimmel
Robert R
RR
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. kimmel@fhcrc.org
Zhao
Lue Ping
LP
Nguyen
Doan
D
Lee
Somnit
S
Aronszajn
Mark
M
Cheng
Chun
C
Troshin
Vladislav P
VP
Abrosimov
Alexander
A
Delrow
Jeffrey
J
Tuttle
R Michael
RM
Tsyb
Anatoli F
AF
Kopecky
Kenneth J
KJ
Davis
Scott
S
Neiman
Paul E
PE
D000293:Adolescent; D000328:Adult; D047852:Chernobyl Nuclear Accident; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping / Q000379:methods*; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007223:Infant; D008297:Male; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011210:Power Plants; D015995:Prevalence; D018788:Radioactive Hazard Release; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods; D013964:Thyroid Neoplasms / Q000235:genetics*; D014455:Ukraine
D004273:DNA, Neoplasm