Deletions of the INK4A gene occur in malignant peripheral nerve sheath tumors but not in neurofibromas Journal Article
| Authors: | Kourea, H. P.; Orlow, I.; Scheithauer, B. W.; Cordon-Cardo, C.; Woodruff, J. M. |
| Article Title: | Deletions of the INK4A gene occur in malignant peripheral nerve sheath tumors but not in neurofibromas |
| Abstract: | The INK4A gene, a candidate tumor suppressor gene located on chromosome 9p21, encodes two protein products, p16 and p19(ARF). p16 is a negative cell cycle regulator capable of arresting cells in the G1 phase by inhibiting cyclin-dependent kinases 4 (Cdk4) and 6 (Cdk6), thus preventing pRB phosphorylation. p19(ARF) prevents Mdm2-mediated neutralization of p53. Loss of INK4A is a frequent molecular alteration involved in the genesis of several neoplasms, including tumors of neuroectodermal origin. This study investigated the frequency of INK4A gene alterations in a series of malignant peripheral nerve sheath tumors (MPNSTs) and neurofibromas (NFs). INK4A gene and the p19(ARF)-specific exon 1β were studied in 11 MPNST samples from 8 patients and 7 neurofibromas. Presence of INK4A deletions was assessed by Southern blotting hybridization and by a multiplex polymerase chain reaction (mPCR). INK4A point mutations were examined by single-strand conformation polymorphism (SSCP) and sequencing. The p16 promoter methylation status was determined by PCR amplification of bisulfite-treated DNA. Homozygous deletions of exon 2, thus affecting both p16 and p19(ARF), were identified in MPNSTs from 4 of 8 patients. Deletions, mutations, or silencing by methylation were not identified in the neurofibromas analyzed. Based on our results, we conclude that INK4A deletions are frequent events in MPNSTs and may participate in tumor progression. Silencing of p16 by methylation, which occurs often in several tumor types, is uncommon in MPNSTs. |
| Keywords: | clinical article; controlled study; human tissue; gene mutation; gene deletion; polymerase chain reaction; gene amplification; cancer genetics; nerve sheath tumor; neurofibroma; southern blotting; single strand conformation polymorphism; human; priority journal; article |
| Journal Title: | American Journal of Pathology |
| Volume: | 155 |
| Issue: | 6 |
| ISSN: | 0002-9440 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 1999-12-01 |
| Start Page: | 1855 |
| End Page: | 1860 |
| Language: | English |
| PUBMED: | 10595915 |
| PROVIDER: | scopus |
| PMCID: | PMC1866948 |
| DOI: | 10.1016/S0002-9440(10)65504-6 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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