A positive selection system designed to identify and recover candidate tumor-suppressor genes is described. The system compares mRNA expression of genes from normal and tumor-derived human mammary epithelial cells grown in a special medium that supports similar growth rates of the two cell types. mRNAs uniquely expressed in normal cells are recovered as cDNAs after subtraction with mRNA from tu...

Most tumor suppressor genes are commonly inactivated in the development of colorectal cancer (CRC). The activation of tumor suppressor genes may be beneficial to suppress the development and metastasis of CRC. This study analyzed genes expression and methylation levels in different stages of CRC. Genes with downregulated mRNA expression and upregulated methylation level in advanced CRC were scr...

Mouse models have provided significant insights into the molecular mechanisms of tumor suppressor gene function. Here we use mouse models of prostate carcinogenesis to demonstrate that the Nkx3.1 homeobox gene undergoes epigenetic inactivation through loss of protein expression. Loss of function of Nkx3.1 in mice cooperates with loss of function of the Pten tumor suppressor gene in cancer progr...

We examined 18 atypical teratoid and rhabdoid tumors of the brain and 7 renal and 4 extrarenal rhabdoid tumors for mutations in the candidate rhabdoid tumor suppressor gene, INI1. Fifteen tumors had homozygous deletions of one or more exons of the INI1 gene, and the other 14 tumors demonstrated mutations. Germ-line mutations of INI1 were identified in four children, one with an atypical teratoi...

Evidence from cytogenetics, multipoint linkage analyses of familial melanoma, and loss of heterozygosity studies of familial and sporadic melanomas support localization of a melanoma susceptibfflty or tumor suppressor gene at chromosomal region 9p21—23. Recently, the inhibitor of cydlin-dependent kinase 4 (CDK4I; also known as p16@'4, multiple tumor suppressor 1, or CDKN2 gene) has been mappe...

Evidence from cytogenetics, multipoint linkage analyses of familial melanoma, and loss of heterozygosity studies of familial and sporadic melanomas support localization of a melanoma susceptibfflty or tumor suppressor gene at chromosomal region 9p21—23. Recently, the inhibitor of cydlin-dependent kinase 4 (CDK4I; also known as p16@'4, multiple tumor suppressor 1, or CDKN2 gene) has been mappe...

TP53 is the most commonly mutated tumor suppressor gene and its mutation drives tumorigenesis. Using ChIP-seq for p53 in the absence of acute cell stress, we found that wild-type but not mutant p53 binds and activates numerous tumor suppressor genes, including PTEN, STK11(LKB1), miR-34a, KDM6A(UTX), FOXO1, PHLDA3, and TNFRSF10B through consensus binding sites in enhancers and promoters. Depleti...

Loss of heterozygosity on chromosome 11q23 is observed at high frequency in human nonsmall cell lung carcinomas (NSCLCs), suggesting the presence of a tumor suppressor gene. Previous analysis of DNA from 79 patients identified a commonly deleted segment of 5 centimorgans. Complementation analysis was used to further localize a putative tumor suppressor gene. Three yeast artificial chromosome (Y...

The observation that mutations in tumor suppressor genes can have haploinsufficient, as well as gain of function and dominant negative, phenotypes has caused a reevaluation of the 'two-hit' model of tumor suppressor inactivation. Here we examine the history of haploinsufficiency and tumor suppressors in order to understand the origin of the 'two-hit' dogma. The two-hit model of tumor suppressor...