TP53, p14ARF, p16INK4a and H-ras gene molecular analysis in intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses.
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.
Perrone
Federica
F
Unit of Experimental Molecular Pathology, Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Oggionni
Maria
M
Birindelli
Sarah
S
Suardi
Simona
S
Tabano
Silvia
S
Romano
Roberta
R
Moiraghi
Maria Luisa
ML
Bimbi
Gabriella
G
Quattrone
Pasquale
P
Cantu
Giulio
G
Pierotti
Marco A
MA
Licitra
Lisa
L
Pilotti
Silvana
S
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D019942:Genes, p16; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009669:Nose Neoplasms / Q000235:genetics* / Q000473:pathology; D010255:Paranasal Sinus Neoplasms / Q000235:genetics* / Q000473:pathology; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
D025803:Tumor Suppressor Protein p14ARF; D004247:DNA