A Robertsonian translocation suppresses a somatic recombination pathway to loss of heterozygosity

Nat Genet. 2003 Jan;33(1):33-9. doi: 10.1038/ng1055. Epub 2002 Nov 25.


In mammals, loss of APC/Apc gatekeeper function initiates intestinal tumorigenesis. Several different mechanisms have been shown or proposed to mediate functional loss of APC/Apc: mutation in APC/Apc, non-disjunction, homologous somatic recombination and epigenetic silencing. The demonstration that, in the C57BL/6 (B6) Apc(Min/+) mouse model of inherited intestinal cancer, loss of Apc function can occur by loss of heterozygosity (LOH) through somatic recombination between homologs presents an opportunity to search for polymorphisms in the homologous somatic recombination pathway. We report that the Robertsonian translocation Rb(7.18)9Lub (Rb9) suppresses the multiplicity of intestinal adenomas in this mouse model. As the copy number of Rb9 increases, the association with the interphase nucleolus of the rDNA repeats centromeric to the Apc locus on Chromosome 18 is increasingly disrupted. Our analysis shows that homologous somatic recombination is the principal pathway for LOH in adenomas in B6 Apc(Min/+) mice. These studies provide additional evidence that neoplastic growth can initiate in the complete absence of canonical genomic instability.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoma / genetics
  • Adenoma / pathology
  • Animals
  • Cell Division
  • Chromosomes, Mammalian / genetics
  • Disease Models, Animal
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic
  • Genes, APC
  • Genes, Dominant / genetics
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Intestinal Neoplasms / genetics
  • Intestinal Neoplasms / pathology
  • Loss of Heterozygosity / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Recombination, Genetic / genetics*
  • Translocation, Genetic / genetics*

Associated data

  • OMIM/175100