These results are consistent with the idea that p16 allelic variants that decrease Cdk interaction predispose individuals who carry them to an increased risk of cancer.
Furthermore, CDKN2 mRNA levels were similar in the 9 cancer cell lines that retain CDKN2, as compared to normal human ovarian surface epithelial cell lines.
To investigate whether CDKN2B and CDKN2 are involved in esophageal tumorigenesis, we studied homozygous deletion, intragenic mutation, and messenger RNA (mRNA) expression of CDKN2 and CDKN2B in nine esophageal squamous cancer cell lines.
One half of all cancer cell lines and one fourth of lung cancer cell lines examined to date contain homozygous deletions (i.e., both alleles lost) of CDKN2.
These results: (i) demonstrate that the phosphorylase deficiency is distributed among almost all the most important human cancers; (ii) confirm and extend the tumor types were p16INK4 gene inactivation is observable and (iii) suggest that deletions at 9p21 (in humans) or at syntenic chromosomes (in other species) might represent a general mechanism of p16INK4 gene loss of function and possibly, in turn, of cancer development and/or progression.
The tumor suppressor genes p16INK4A and p15INK4B map to the 9p21 chromosomal locus and are either homozygously deleted or mutated in a wide range of human cancer cell lines and tumors.
Our data confirm the predicted reciprocity between Rb inactivation and p16 expression in a common human malignancy and define differential p16 expression as a fundamental distinction between NSCLC and SCLC.
Our findings suggest that homozygous deletion of the p16 gene is seen in about 15% of ALL cases, is not restricted to cases with cytogenetically detectable 9p deletion, and could have a pathogenetic role in this malignancy.
Recent data suggest that homozygous deletion of the cyclin-dependent kinase 4 inhibitor gene (CDKN2), a putative tumour suppressor gene located on chromosome 9p21, represents a common genetic event in human cancer.
Molecular genetic studies have revealed that deletion of the p16 and p15 genes occurs frequently in cancer cell lines and in certain malignant neoplasms.
We analysed the DNAs from 37 gliomas of several grades of malignancy for allelic loss of chromosome 9p and aberrations of the MTS1/p16 and MTS2/p15 genes.
We determined the prevalence of allelic loss at 9p21 and mutations in CDKN2 in esophageal adenocarcinomas and investigated the order in which they occurred relative to the development of aneuploidy and cancer during neoplastic progression.
The high incidence of p16(INK4A) gene deletions in pediatric T cell lineage ALL suggests that this genetic alteration could represent an early and key event in the development of such a malignancy but it should not have any prognostic value.
We previously reported that p16 levels are low to undetectable in normal human uroepithelial cells (HUCs) and in immortalized uroepithelial cells with functional pRb, whereas p16 levels are markedly elevated in immortal HUCs with altered pRb (T. Yeager et al., Cancer Res., 55: 493-497, 1995).
A variety of cancer syndromes involving the P16 and BRCA2 genes, for example, also lead to pancreatic cancer, but the gene responsible for familial pancreatic cancer has not been identified so far.
The p16INK4a gene is frequently inactivated in human tumors, and inheritance of mutant alleles results in susceptibility to several types of cancer. p16INK4a is part of a cell-cycle regulatory pathway that converges in the tumor suppressor protein Rb.