Haploinsufficient tumor suppressor genes.

Haploinsufficiency of tumor suppressor genes (TSGs) indicates that the reduced levels of proteins in cells that lack one allele of the genomic locus results in the inability of the cell to execute normal cellular functions contributing to tumor development. Representative cases of haploinsufficient TSGs are and . Tumor development is significantly accelerated in both mice with homozygous and heterozygous gene deletion, with expression of the wild type allele in the latter. Newly characterized TSGs such as and have also shown haploid insufficiency for tumor suppression. This phenotype has typically been demonstrated in gene knockout mouse models, but analyses of human samples have been conducted in some cases. Recent studies suggest collaboration of multiple haploinsufficient TSGs in 5q-, 7q-, and 8q- syndromes, which is called compound haploinsufficiency. Although is a classical TSG, it also belongs to this category since accelerates tumor development when both alleles for are inactivated. Haploid insufficiency of was also reported in myeloid leukemogenesis in the presence of inv(16). In case of p53, cells achieve only ~25% of p53 mRNA and protein levels as compared to those in wild type, which could explain the mechanism. collaborates with in colorectal cancer development; and collaborates with mutation in pancreatic ductal adenocarcinomagenesis, demonstrating the synergism of haploinsufficient TSGs and other oncogenic events. These TSGs can be targets for activation therapy in cancer since they retain a functional allele even in tumor cells.