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March 2007, SoftGenetics - Loss of Heterozygosity Detection with GeneMarker ®:

Introduction

Loss of Heterozygosity (LOH) occurs when a somatic cell contains only one copy of an allele due to non-disjunction during mitosis, segregation duringrecombination, or deletion of a chromosome segment. LOH becomes critical when the remaining allele contains a point mutation that renders the geneinactive. This is a common occurrence in cancers where a tumor suppressor gene is affected. Tumor suppressor genes code for proteins that regulatethe cell’s life cycle. Thus, they are critical in preventing tumor formation. The human retinoblastoma (pRb) was the first tumor suppressor protein foundto be dysfunctional in a number of types of cancer (1). Another protein, tumor protein 53 (TP53), is central to many of the cell’s anti-cancermechanisms. It plays a role in apoptosis, genetic stability, and inhibition of angiogenesis (2). It has also been found that TP53 is involved in the DNArepair support function of pRb, thus linking these two cancer regulating pathways (3).
Recently, a vaccine that prevents women from contracting human papillomavirus (HPV) has been developed for use in the United States (4). Thesignificance of this vaccine is that it has the potential to prevent cervical cancer. Cells infected with HPV produce oncogenic proteins that can bind withand inactivate the pRb protein. Since one of the major functions of the pRb protein is to prevent cells from dividing it is a key factor in regulating thecell cycle. Without this specific protein, a cell will continue to divide and become cancerous (5). Examples of other major cancers caused by loss ofheterozygosity include breast, ovarian, and colorectal cancer (6, 7, 8).
GeneMarker fragment analysis software has been developed to aid researchers and clinicians in the detection of LOH within cancer cells. Using a uniqueallele calling algorithm, GeneMarker uses the germ line reference to compare and detect LOH in patient samples.

 

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