Aneuploidy: Using genetic instability to preserve a haploid genome?
Aneuploidy occurs in many cancers, and is a sign of genetic instability in the genome.
We use two different techniques- single nucleotide polymorphisms (SNPs) and gene
expression arrays to investigate two aspects of aneuploidy- the pattern of genetic
instability causing aneuploidy, and the reason aneuploidy occurs. SNP technology was
employed to obtain areas of loss of heterozygosity (LOH) in a prostate cancer cell line
(DU-145), as a means of looking at genetic instability. Using a novel method of analysis
we were able to eliminate noise in both normal and cancer samples, and to visualize
large quantities of data in a graphical manner. We observed several areas of genetic
instability that can be linked to the cancer phenotype. Using gene expression arrays, we
investigated the expression of genes in 210 human cell lines and 2,035 human tissues of
multiple origins, both cancer and normal, to look at why aneuploidy occurs. We found
778 genes that are commonly expressed in all 2,245 samples, are distributed throughout
the human genome, and have mostly metabolic functions, indicating that these are
housekeeping genes or universally expressed genes for cell growth and survival.
Additionally, we found a subset of variably expressed genes, from where tissue specific
genes were also chosen and investigated. We looked at prostate specific tissues, and
found that there were some genes that were more highly expressed in the prostate
tissues and cell lines, than in other non-prostate samples. We provide evidence that the
broken chromosomes in the prostate cell lines are retaining specific regions of their
genome, as a means of conserving universally expressed genes, which allows the
maintenance of at least a haploid genome, even in cases where an essential gene is
mutated or non-functional, in the form of translocations.
School:University of Toledo Health Science Campus
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:loss of heterozygosity aneuploidy gene expression single nucleotide polymorphisms snps
Date of Publication:07/14/2009