Everything about Loss Of Heterozygosity totally explained
Loss of heterozygosity (LOH) in a
cell represents the loss of normal function of one allele of a gene in which the other allele was already inactivated. This term is mostly used in the context of oncogenesis; after an inactivating mutation in one allele of a tumor suppressor gene occurs in the parent's germline cell, it's passed on to the zygote resulting in an offspring that's heterozygous for that allele. In oncology, loss of heterozygosity occurs when the remaining functional allele in a somatic cell of the offspring becomes inactivated by mutation. This results in no normal tumor suppressor being produced (or no tumor suppressor being produced at all) and almost certainly results in tumorigenesis.
In cancer
It is a common occurrence in
cancer, where it indicates the absence of a functional
tumor suppressor gene in the lost region. However, many people remain healthy with such a loss, because there still is one functional gene left on the other chromosome of the
chromosome pair. However, the remaining copy of the tumor suppressor gene can be inactivated by a
point mutation, leaving no tumor suppressor gene to protect the body.
Retinoblastoma
The classical example of such a loss of protecting genes is hereditary
retinoblastoma, in which one parent's contribution of the tumor suppressor Rb1 is flawed. Although most cells will have a functional second copy, chance loss of heterozygosity events in individual cells almost invariably lead to the development of this retinal cancer in the young child.
Detection
Loss of heterozygosity can be identified in cancers by noting the presence of
heterozygosity at a genetic
locus in an organism's
germline DNA, and the absence of heterozygosity at that locus in the cancer cells. This is often done using
polymorphic markers, such as
microsatellites or
single nucleotide polymorphisms, for which the two parents contributed different
alleles.
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