Implications of P16/CDKN2A deletion in pleural mesotheliomas.
Homozygous deletion of P16/CDKN2A is found in approximately 75% of mesotheliomas amd may be the most common genetic alteration in this cancer. In terms of diagnostic applications, its high prevalence makes it a useful marker to distinguish malignant mesothelial cells from benign reactive ones in pleural fluid cytologic preparations. In terms of prognosis, P16/CDKN2A loss is associated with more aggressive clinical behavior in mesotheliomas. The homozygous co-deletion of MTAP, encoding the enzyme methylthioadenosine phosphorylase, in approximately 90% of mesotheliomas with P16/CDKN2A loss has potential therapeutic applications because MTAP-deficient tumors may be responsive to inhibitors of de novo AMP synthesis. Finally, global gene expression profiling using Affymetrix U133A chips finds few gene expression correlates of P16/CDKN2A deletion in pleural mesothelioma, consistent with its non-transcriptional mode of direct action through regulation of cell cycle-related kinase signaling.
Ladanyi
Marc
M
Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. ladanyim@mskcc.org
D003584:Cytological Techniques; D017353:Gene Deletion; D020869:Gene Expression Profiling; D019942:Genes, p16 / Q000502:physiology*; D006801:Humans; D008654:Mesothelioma / Q000235:genetics*; D016066:Pleural Effusion, Malignant; D010997:Pleural Neoplasms / Q000235:genetics*; D011379:Prognosis