Genomic instability in radiation-induced mouse lymphoma from p53 heterozygous mice

Jiang Hua Mao, Jiangzhen Li, Tao Jiang, Qian Li, Di Wu, Jesus Perez-Losada, Reyno DelRosario, Leif E. Peterson, Allan Balmain, Wei Wen Cai

Research output: Contribution to journalArticle

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7924-7934
Number of pages11
JournalOncogene
Volume24
Issue number53
DOIs
StatePublished - Nov 24 2005

Keywords

  • Genomic instability
  • p53
  • Radiation
  • Thymic lymphoma

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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