Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine
phosphorylase gene in the majority of pleural mesotheliomas.
BPDCN, blastic plasmacytoid dendritic cell neoplasm; CDKN, cyclin-dependent kinase inhibitor; MTAP, methylthioadenosine
phosphorylase; TRAF2, tumor necrosis factor receptor-associated factor 2; CARD9, caspase recruitment domain; RB1, retinoblastoma tumor suppressor gene; CYP1A1, cytochrome P450 family 1 subfamily a polypeptide 1; PRKCSH, protein kinase C substrate 80K-H; PTPN23, protein-tyrosine-phosphatase-n23; MCC, mutated in colorectal cancer; APC, adenomatous polyposis coli tumor suppressor gene; PARK2, Parkinson protein 2; MAD1L1, mitotic arrest deficient-like 1; TP53, tumor protein 53.
S-adenosylmethionine and methylthioadenosine
are antiapoptotic in cultured rat hepatocytes but proapoptotic in human hepatoma cells.
Its by-product methylthioadenosine
(MTA) is a natural analgesic and anti-inflammatory.
3) This region contains the coding sequence for two cyclin-dependent kinase inhibitors, CDKN2A and CDKN2B, which play an important role in the regulation of the cell cycle and have been implicated in the pathogenesis of atherosclerosis, as well as for MTAP, a methylthioadenosine
phosphorylase enzyme important in polyamine metabolism and the salvage of adenine and methionine.
Deletion of the 9p21 region is very common in malignant mesotheliomas, typically resulting in loss of p16 (CDKN2A) and its splice variant p14, p15 (CDKN2B), and methylthioadenosine
Of particular interest are 3 of the genes (MGST3, microsomal glutathione S-transferase 3; GBP1, guanylate binding protein 1, interferon-inducible, 67kDa; MTAP, methylthioadenosine
phosphorylase), which have patents that specifically claim the use of nucleotide sequences in hybridization assays.
There is an increasing interest in diagnostic applications of the 9p21 deletion within a cluster of genes that includes cyclin-dependent kinase inhibitor 2A (CDKN2A), cyclin-dependent kinase inhibitor 2B (CDKN2B), and methylthioadenosine
The only other gene in the region, methylthioadenosine
phosphorylase (MTAP), is ubiquitously expressed.
80) One of the most common genetic alterations in mesothelioma is the homozygous deletion of the 9p21 locus within a cluster of genes that includes cyclin-dependent kinase inhibitor 2A (CDKN2A), CDKN2B, and methylthioadenosine
Data on chromosome imbalance could also be useful to design new treatment strategies: a relevant example targets the methylthioadenosine
phosphorylase gene (MTAP).