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• W2181502647 abstract "Purpose: p14 ARF , p15 INK4b , and p16 INK4a are tumor suppressor genes that are located closely at 9p21 and are often coinactivated by genetic or epigenetic alterations. Malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma with poor prognosis. However, the prognostic implications of inactivation of p14 ARF , p15 INK4b , and p16 INK4a in MPNSTs have not been adequately investigated. Here we carried out a genetic, epigenetic, and expression analysis of p14 ARF , p15 INK4b , and p16 INK4a , and clarified the prognostic significance of their inactivation in MPNSTs. Experimental Design: p14 ARF , p15 INK4b , and p16 INK4a protein expressions were assessed by immunohistochemistry in 129 formalin-fixed samples of MPNST including 85 primary tumors. Thirty-nine samples, for which frozen material was available, were also investigated by Western blotting and quantitative reverse transcription PCR (RT-PCR) to detect p14 ARF , p15 INK4b , and p16 INK4a protein and mRNA expression, and by multiplex real-time PCR, PCR single strand conformation polymorphism and methylation-specific PCR to detect p14 ARF , p15 INK4b , and p16 INK4a gene alterations. Results: Immunohistochemically decreased expressions of p14 ARF , p15 INK4b , and p16 INK4a were observed in 48%, 54%, and 49% of primary MPNSTs, respectively, and were significantly correlated with their concordant mRNA levels. As for gene alterations, homozygous deletion of CDKN2A was detected in one third of the cases. Inactivation of p14 ARF and p16 INK4a was associated with poor prognosis by both univariate and multivariate analyses. Furthermore, cases with inactivation of all p14 ARF , p15 INK4b , and p16 INK4a genes showed the worst prognosis in a combined prognostic assessment. Conclusion: A comprehensive analysis of p14 ARF , p15 INK4b , and p16 INK4a inactivation status provides useful prognostic information in MPNSTs. Clin Cancer Res; 17(11); 3771–82. � 2011 AACR." @default.
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• W2181502647 date "2011-01-01" @default.
• W2181502647 modified "2023-10-06" @default.
• W2181502647 title "Imaging, Diagnosis, Prognosis Prognostic Significance of p14 ARF , p15 INK4b , and p16 INK4a Inactivation in Malignant Peripheral Nerve Sheath Tumors" @default.
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