title: Genomic instability in radiation-induced mouse lymphoma from p53 heterozygous mice.
abstract: Although radiation can directly induce DNA damage and is a known human and animal carcinogen, the number of genetic changes in radiation-induced tumors, and the pathways responsible for generating them, are unknown. We have used high-density BAC arrays covering >95% of the mouse genome for analysis of genomic patterns of aberrations in spontaneous and radiation-induced mouse lymphomas. The majority of radiation-induced tumors exhibit one of three 'signatures' based on gene copy number changes. Some exhibit extensive scrambling of the genome, with very high numbers of recurrent gains and losses. Two other signatures are characterized by excess gains but relatively few losses, or vice versa. Changes in spontaneous tumors often involve whole chromosomes, whereas radiation-induced tumors exhibit a high frequency of localized deletion/amplification events. The number of copy number abnormalities does not correlate with the latency or pathology of the tumors. We propose that specific early events following radiation exposure induce changes in 'caretaker' genes that control specific downstream pathways involved in DNA damage repair. The nature of these early events may determine the overall genomic signature observed in the resulting tumor.
authors.affiliation: Cancer Research Institute, University of California at San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jiang-Hua
authors.initials: JH
authors.lastname: Mao
authors.forename: Jiangzhen
authors.initials: J
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Jesus
authors.initials: J
authors.lastname: Perez-Losada
authors.forename: Reyno
authors.initials: R
authors.lastname: DelRosario
authors.forename: Leif
authors.initials: L
authors.lastname: Peterson
authors.forename: Allan
authors.initials: A
authors.lastname: Balmain
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Cai
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D020869:Gene Expression Profiling; D016158:Genes, p53; D042822:Genomic Instability / Q000528:radiation effects*; D008223:Lymphoma / Q000209:etiology* / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D013953:Thymus Neoplasms / Q000209:etiology / Q000235:genetics*