Loss of heterozygosity
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 is passed on to the zygote resulting in an offspring that is 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 and almost certainly results in tumorigenesis.
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.
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.
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.