TP53, P14ARF, P16INK4a and H-ras gene molecular analysis in intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses

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, p14ARF and p16INK4a 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 p14ARF alterations accounted for 88% and the evidence p16INK4a 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 17p 13 and an uncommon high rate of p53 stabilization were detected in 58% and 59% of the cases, respectively. p14ARF and p16INK4a 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 p16INK4a alterations shared TP53 or p14ARF deregulation. The present results show a close association of this occupational tumor with TP53, p14ARF and p16INK4a 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.