Faculty Collaboration Database

Genomic instability in mouse Burkitt lymphoma is dominated by illegitimate genetic recombinations, not point mutations. Oncogene 2002 Oct 17;21(47):7235-40

Date

10/09/2002

Pubmed ID

12370814

DOI

10.1038/sj.onc.1205697

Scopus ID

2-s2.0-0037126384 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

lambda-MYC-induced mouse Burkitt lymphoma (BL) harboring the shuttle vector pUR288, which includes a lacZ reporter gene to study mutagenesis, was employed to assess genomic instability associated with MYC deregulation. The frequency of lacZ mutations in lymphomas was elevated only 1.75-fold above that in normal tissue, indicating that mouse BL does not exhibit a phenotype of hypermutability. However, the nature of lacZ mutations was strikingly different in normal tissues and lymphomas. While point mutations comprised approximately 75% of the mutations found in normal tissues, apparent translocations, deletions and inversions constituted the majority of mutations ( approximately 65%) in lymphomas. Genomic instability in mouse BL thus seems characterized by a preponderance of illegitimate genetic rearrangements in the context of near-background mutant frequencies. SKY analyses of cell lines from primary BL tumors revealed substantial changes in chromosomal structure, confirming the lacZ studies. Bi-allelic deletions of the tumor suppressor p16(Ink4a) were detected in six out of 16 cell lines, illustrating cellular selection of advantageous mutations. Together, these approaches indicate that MYC may contribute to lymphomagenesis through the dominant mutator effect of inducing chromosomal instability. The results further suggest that a phenotype of hypermutability (elevated mutant frequency) may not always be required for oncogenesis to occur.

Author List

Rockwood LD, Torrey TA, Kim JS, Coleman AE, Kovalchuk AL, Xiang S, Ried T, Morse HC 3rd, Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Burkitt Lymphoma
Cell Line
Genes, Immunoglobulin
Genes, Reporter
Genes, myc
Genes, p16
Lac Operon
Mice
Mice, Transgenic
Point Mutation
Recombination, Genetic