Loss of Heterozygosity

Loss of heterozygosity (LOH) is a common form of allelic imbalance by which a heterozygous somatic cell becomes homozygous because one of the two alleles gets lost. This form of chromosome instability is sufficient to provide selective growth advantage and has been recognized as a major cause of tumorigenesis. In 1929, the genetic mechanism of LOH was explained for the first time by studying mutant spots induced by X-rays in Drosophila melanogaster. Later on, the detection of LOH has been used to identify genomic regions that harbor putative tumor suppressor genes and to characterize different tumor types, pathological stages, and progression. This identification has provided important insight into the molecular mechanisms of malignant transformation and may deliver the targets for future therapy. Screening for LOH can be performed at polymorphic markers in tumor tissue and ‘liquid biopsies’ and be a promising diagnostic and prognostic tool.