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.
For more details, download the Loss
of Heterozygosity Detection PDF 
(188 Kb)
