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Myc Oncogene-Induced Genomic Instability: DNA Palindromes in Bursal Lymphomagenesis

Genetic instability plays a key role in the formation of naturally occurring cancer. The formation of long DNA palindromes is a rate-limiting step in gene amplification, a common form of tumor-associated genetic instability. Genome-wide analysis of palindrome formation (GAPF) has detected both exten...

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Autores principales: Neiman, Paul E., Elsaesser, Katrina, Loring, Gilbert, Kimmel, Robert
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2444050/
https://www.ncbi.nlm.nih.gov/pubmed/18636108
http://dx.doi.org/10.1371/journal.pgen.1000132
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author Neiman, Paul E.
Elsaesser, Katrina
Loring, Gilbert
Kimmel, Robert
author_facet Neiman, Paul E.
Elsaesser, Katrina
Loring, Gilbert
Kimmel, Robert
author_sort Neiman, Paul E.
collection PubMed
description Genetic instability plays a key role in the formation of naturally occurring cancer. The formation of long DNA palindromes is a rate-limiting step in gene amplification, a common form of tumor-associated genetic instability. Genome-wide analysis of palindrome formation (GAPF) has detected both extensive palindrome formation and gene amplification, beginning early in tumorigenesis, in an experimental Myc-induced model tumor system in the chicken bursa of Fabricius. We determined that GAPF-detected palindromes are abundant and distributed nonrandomly throughout the genome of bursal lymphoma cells, frequently at preexisting short inverted repeats. By combining GAPF with chromatin immunoprecipitation (ChIP), we found a significant association between occupancy of gene-proximal Myc binding sites and the formation of palindromes. Numbers of palindromic loci correlate with increases in both levels of Myc over-expression and ChIP-detected occupancy of Myc binding sites in bursal cells. However, clonal analysis of chick DF-1 fibroblasts suggests that palindrome formation is a stochastic process occurring in individual cells at a small number of loci relative to much larger numbers of susceptible loci in the cell population and that the induction of palindromes is not involved in Myc-induced acute fibroblast transformation. GAPF-detected palindromes at the highly oncogenic bic/miR-155 locus in all of our preneoplastic and neoplastic bursal samples, but not in DNA from normal and other transformed cell types. This finding indicates very strong selection during bursal lymphomagenesis. Therefore, in addition to providing a platform for gene copy number change, palindromes may alter microRNA genes in a fashion that can contribute to cancer development.
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spelling pubmed-24440502008-07-18 Myc Oncogene-Induced Genomic Instability: DNA Palindromes in Bursal Lymphomagenesis Neiman, Paul E. Elsaesser, Katrina Loring, Gilbert Kimmel, Robert PLoS Genet Research Article Genetic instability plays a key role in the formation of naturally occurring cancer. The formation of long DNA palindromes is a rate-limiting step in gene amplification, a common form of tumor-associated genetic instability. Genome-wide analysis of palindrome formation (GAPF) has detected both extensive palindrome formation and gene amplification, beginning early in tumorigenesis, in an experimental Myc-induced model tumor system in the chicken bursa of Fabricius. We determined that GAPF-detected palindromes are abundant and distributed nonrandomly throughout the genome of bursal lymphoma cells, frequently at preexisting short inverted repeats. By combining GAPF with chromatin immunoprecipitation (ChIP), we found a significant association between occupancy of gene-proximal Myc binding sites and the formation of palindromes. Numbers of palindromic loci correlate with increases in both levels of Myc over-expression and ChIP-detected occupancy of Myc binding sites in bursal cells. However, clonal analysis of chick DF-1 fibroblasts suggests that palindrome formation is a stochastic process occurring in individual cells at a small number of loci relative to much larger numbers of susceptible loci in the cell population and that the induction of palindromes is not involved in Myc-induced acute fibroblast transformation. GAPF-detected palindromes at the highly oncogenic bic/miR-155 locus in all of our preneoplastic and neoplastic bursal samples, but not in DNA from normal and other transformed cell types. This finding indicates very strong selection during bursal lymphomagenesis. Therefore, in addition to providing a platform for gene copy number change, palindromes may alter microRNA genes in a fashion that can contribute to cancer development. Public Library of Science 2008-07-18 /pmc/articles/PMC2444050/ /pubmed/18636108 http://dx.doi.org/10.1371/journal.pgen.1000132 Text en Neiman et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Neiman, Paul E.
Elsaesser, Katrina
Loring, Gilbert
Kimmel, Robert
Myc Oncogene-Induced Genomic Instability: DNA Palindromes in Bursal Lymphomagenesis
title Myc Oncogene-Induced Genomic Instability: DNA Palindromes in Bursal Lymphomagenesis
title_full Myc Oncogene-Induced Genomic Instability: DNA Palindromes in Bursal Lymphomagenesis
title_fullStr Myc Oncogene-Induced Genomic Instability: DNA Palindromes in Bursal Lymphomagenesis
title_full_unstemmed Myc Oncogene-Induced Genomic Instability: DNA Palindromes in Bursal Lymphomagenesis
title_short Myc Oncogene-Induced Genomic Instability: DNA Palindromes in Bursal Lymphomagenesis
title_sort myc oncogene-induced genomic instability: dna palindromes in bursal lymphomagenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2444050/
https://www.ncbi.nlm.nih.gov/pubmed/18636108
http://dx.doi.org/10.1371/journal.pgen.1000132
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