Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma

Citation
T. Tsuchiya et al., Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma, CANC GENET, 120(2), 2000, pp. 91-98
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CANCER GENETICS AND CYTOGENETICS
ISSN journal
0165-4608 → ACNP
Volume
120
Issue
2
Year of publication
2000
Pages
91 - 98
Database
ISI
SICI code
0165-4608(20000715)120:2<91:AOTPPP>2.0.ZU;2-H
Abstract
We examined alterations of the p16INK4, p14ARF, p15, TP53, and MDM2 genes i n 30 osteosarcomas and 24 Ewing sarcomas. Among 21 osteosarcomas and 24 Ewi ng sarcomas, p16INK4, p14ARF, and p15 abnormalities were found in 4 (19%), 2 (9%), and 3 (14%) osteosarcomas, respectively, and in 4 (17%), 3 (13%), a nd 4 (17%) Ewing sarcomas, respectively. The alterations of p16INK4, p14ARF , and p15 included homozygous deletions spanning all 3 genes, methylation o f p16INK4 or p15, and a nonsense mutation of p16INK4, which simultaneously caused a missense mutation of p14ARF. Alterations of TP53 were found in 15 (50%) of 30 osteosarcomas and 1 (3%) of 24 Ewing sarcomas. None of the sarc omas showed MDM2 amplification. While TP53 abnormalities were far more freq uent in osteosarcoma than in Ewing sarcoma, alterations of p16INK4, p14ARF, and p15 were present at similar frequencies in the two types of sarcoma. T he event-free survival (EFS) was worse in Ewing sarcoma patients with p16IN K4 and p14ARF mutation/deletion than in those without the mutation/deletion (P = 0.019), and EFS was worse in osteosarcoma patients with TP53 alterati ons than in those without TP53 alterations (P = 0.048). The different incid ence of TP53 abnormalities in the 2 types of sarcoma may reflect difference s of the molecular processes through which the 2 types of tumor develop. (C ) 2000 Elsevier Science Inc. All rights reserved.