PMID: 9443039Jan 27, 1998Paper

Chromosome loss with concomitant duplication and recombination both contribute most to loss of heterozygosity in vitro

Genes, Chromosomes & Cancer
A G de Nooij-Van DalenM Giphart-Gassler

Abstract

Loss of heterozygosity (LOH) plays an important role in the expression of recessive mutations in mammalian cells. To gain insight into the rate and mechanisms of LOH the autosomal HLA-A gene was used as a model system. Spontaneous HLA-A2 mutants originated with a rate of respectively 4.1 x 10(-6) and 6.9 x 10(-6) per cell per generation in TK6 and WI-L2-NS, two isogenic lymphoblastoid cell lines which differ in TP53 status. The rate of loss of HLA-A2 is 10-50 times higher compared to the mutation rate of the X-linked HPRT gene. The homozygous TP53 mutation in WI-L2-NS had no effect on the rate of HLA-A2 loss or the spectrum of these mutations. Microsatellite analysis of most of the HLA-A2 mutants (84%) showed LOH for multiple markers on chromosome arm 6p telomeric of a recombination breakpoint, LOH for all 6p markers, or LOH for markers on both the 6p- and 6q-arms. Cytogenetic analysis showed that these mechanisms gave mutant cells which harbored two intact chromosomes 6 and which were indistinguishable from non-mutant cells. Therefore, loss of HLA-A2 is mainly caused by somatic recombination (33-50%) or chromosome loss with duplication of the remaining chromosome (34-40%). These findings correspond to the mechanisms behind los...Continue Reading

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Citations

May 8, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·W P Robinson
Nov 14, 2000·Teratogenesis, Carcinogenesis, and Mutagenesis·C MonteiroJ A Armour
Mar 10, 2001·Genes, Chromosomes & Cancer·A G de Nooij-Van DalenM Giphart-Gassler
Oct 16, 2007·Cancer Immunology, Immunotherapy : CII·Rosa MéndezFederico Garrido
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Aug 30, 2020·Nature Communications·Hui XuYing-Jin Yuan

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