Asbestos Research Today is a free monthly online journal that collates and summarizes the latest research about Asbestos, including details on mesothelioma, lung disease, dangers, effects, risks.

Implications of P16/CDKN2A deletion in pleural mesotheliomas.

Ladanyi M

Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. ladanyim@mskcc.org

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.

Published 13 June 2005 in Lung Cancer, 49: S95-8.
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