Deletions of the INK4A Gene Occur in Malignant Peripheral Nerve Sheath Tumors but not in Neurofibromas

摘要: The INK4A gene, a candidate tumor suppressor gene located on chromosome 9p21, encodes two protein products, p16 and p19ARF. is negative cell cycle regulator capable of arresting cells in the G1 phase by inhibiting cyclin-dependent kinases 4 (Cdk4) 6 (Cdk6), thus preventing pRB phosphorylation. p19ARF prevents Mdm2-mediated neutralization p53. Loss frequent molecular alteration involved genesis several neoplasms, including tumors neuroectodermal origin. This study investigated frequency alterations series malignant peripheral nerve sheath (MPNSTs) neurofibromas (NFs). p19ARF-specific exon 1β were studied 11 MPNST samples from 8 patients 7 neurofibromas. Presence deletions was assessed Southern blotting hybridization multiplex polymerase chain reaction (mPCR). point mutations examined single-strand conformation polymorphism (SSCP) sequencing. promoter methylation status determined PCR amplification bisulfite-treated DNA. Homozygous 2, affecting both p19ARF, identified MPNSTs patients. Deletions, mutations, or silencing not analyzed. Based our results, we conclude that are events may participate progression. Silencing methylation, which occurs often types, uncommon MPNSTs.