title: A model for genetic complementation controlling the chromosomal abnormalities and loss of heterozygosity formation in cancer.
abstract: The relationship between the apparently random chromosomal changes found in aneuploidy and the genetic instability driving the progression of cancer is not clear. We report a test of the hypothesis that aneuploid chromosomal abnormalities might be selected to preserve cell-survival genes during loss of heterozygosity (LOH) formations which eliminate tumor suppressor genes. The LOHs and structurally abnormal chromosomes present in the aneuploid LoVo (colon), A549 (lung), SUIT-2 (pancreas), and LN-18 (glioma) cancer cell lines were identified by single nucleotide polymorphisms (SNPs) and Spectral Karyotyping (SKY). The Mann-Whitney U and chi square tests were used to evaluate possible differences in chromosome numbers and abnormalities between the cell lines, with two-tailed P values of <0.01 being considered significant. The cell lines differed significantly in chromosome numbers and frequency of structurally abnormal chromosomes. The SNP analysis revealed that each cell line contained at least a haploid set of somatic chromosomes, consistent with our hypothesis that cell-survival genes are widely scattered throughout the genome. Further, over 90% of the chromosomal abnormalities seemed to be selected, often after LOH formation, for gene-dosage compensation or to provide heterozygosity for specific chromosomal regions. These results suggest that the chromosomal changes of aneuploidy are not random, but may be selected to provide gene-dosage compensation and/or retain functional alleles of cell-survival genes during LOH formation.
authors: Department of Surgery and The University of Toledo Advanced Microscopy and Imaging Center, The University of Toledo, Health Science Campus Toledo, Toledo, OH 43614-5804, USA.
authors: A L
authors: AL
authors: Nestor
authors: S L
authors: SL
authors: Hollopeter
authors: S-I
authors: SI
authors: Matsui
authors: D
authors: D
authors: Allison
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D018628:Gene Dosage; D005816:Genetic Complementation Test; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D032681:Spectral Karyotyping; D014178:Translocation, Genetic