Loss of heterozygosity

Loss of heterozygosity, or LOH for short, refers to the loss of normal function of the allele of one gene in a cell in which the other allele was already inactivated.

In pathology and specifically in tumor biology, LOH is an important explanatory mechanism for the development of certain tumors (oncogenesis).

In almost all malignant as well as in some benign tumors, chromosomal gains and losses of certain chromosomal regions are found in a comparison with normal cells. In the case of deletions , one allele is usually missing, i.e. the hereditary formation of one parent. This is called loss of heterozygosity. Loss of heterozygosity plays a particularly important role in the inactivation of tumor suppressor genes.

Retinoblastoma (tumor in the retina of the eye): Here, a defect on one chromosome is inherited, and the defect can only lead to tumor formation when the second gene is also mutated (second hit) by external factors (such as chemical carcinogens or even radiation) (Mendoza PR et al. 2015).

Furthermore, characteristic deletions with diagnostic and prognostic relevance in acute myeloid leukemias are found, e.g. losses on the long arm of chromosome 5 (5q-) or the loss of chromosome 7.

1. Mendoza PR et al (2015) The Biology of Retinoblastoma. Prog Mol Biol Transl Sci 134:503-516.
2. Wang LH et al (2018) Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview. Cell Physiol Biochem. 51:2647-2693.