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TP53 , p14 ARF , p16 INK4a and H‐ ras gene molecular analysis in intestinal‐type adenocarcinoma of the nasal cavity and paranasal sinuses
Author(s) -
Perrone Federica,
Oggionni Maria,
Birindelli Sarah,
Suardi Simona,
Tabano Silvia,
Romano Roberta,
Moiraghi Maria Luisa,
Bimbi Gabriella,
Quattrone Pasquale,
Cantu Giulio,
Pierotti Marco A.,
Licitra Lisa,
Pilotti Silvana
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11062
Subject(s) - cancer research , gene , locus (genetics) , adenocarcinoma , biology , apoptosis , microbiology and biotechnology , dna methylation , methylation , genetics , gene expression , cancer
Abstract Intestinal‐type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinuses is an uncommon tumor associated with occupational exposure to dusts of different origin. Few investigations addressed molecular alterations in ITAC mainly focused on TP53 , K‐ ras and H‐ ras gene mutations. The occurrence of TP53 , p14 ARF and p16 INK4a deregulation and H‐ ras mutations was investigated in 21 consecutive and untreated ITACs cases, 17 with known professional exposure. No H‐ ras mutations were found. In patients with known exposure, cumulative evidence of TP53 or p14 ARF alterations accounted for 88% and the evidence of p16 INK4a alterations for 65%, respectively. TP53 mutations were present in 44% of the ITACs, consisted of G:C→A:T transitions in 86%, and involved the CpG dinucleotides in 50% of the cases. LOH at the locus 17p13 and an uncommon high rate of p53 stabilization were detected in 58% and 59% of the cases, respectively. p14 ARF and p16 INK4a promoter methylation accounted for 80% and 67% respectively, and LOH at the locus 9p21 occurred in 45% of the cases. Interestingly, all dust‐exposed tumors with p16 INK4a alterations shared TP53 or p14 ARF deregulation. The present results show a close association of this occupational tumor with TP53 , p14 ARF and p16 INK4a gene deregulation. Given the important role that these genes play in cell growth control and apoptosis, the knowledge of ITAC genetic profile may be helpful in selecting more tailored treatments. © 2003 Wiley‐Liss, Inc.