Aberrant p16 expression is correlated with hemizygous deletions at the 9p21-22 chromosome region in non-small cell lung carcinomas.

摘要: The p16 protein is encoded by the CDKN2 gene, and functions as an inhibitor of cyclin-dependent kinase 4 6 (CDK4/6). Phosphorylation retinoblastoma (pRb) CDK4/6 represents a vital step in cell cycle progression. Alterations INK4A are frequent events human malignancies. In non-small lung carcinoma (NSCLC) data concerning mechanisms INK4 inactivation suggest that point mutations aberrant methylation its promoter can only account for proportion cases with abnormal immunoexpression. role deletions this procedure not yet clarified. order to gain more insight into deregulated expression, we investigated state chromosomal region 9p21-22 series 57 NSCLCs, performing detailed mapping analysis, using tight cluster highly polymorphic microsatellite markers, correlating findings immunostaining. Abnormal expression was observed 46% NSCLCs examined. No relationship between staining various clinicopathological parameters. strongly associated hemizygous at IFNA D9S171 loci, which demarcate encoding gene (P=0.002). These involved multistage process NSCL carcinogenesis may represent predominant mechanism inactivation. A significant percentage also LOH noticed D9S162 (35%) D9S126 (38%) loci lie 6cM 4cM, respectively, far from area encodes lNK4A , implying other tumor suppressor genes (TSGs) reside region. Although overall incidence examined high (58%), did observe any correlation smoking habits, histology lymph node status. Another noteworthy finding existence instability (MI) 11% patients. MI provides marker replication error phenotype (RER+), recently defined manifestation genetic wide range tumors. conclusion, alterations (LOH+MI) chromosome affect directly or indirectly p16.