Proto-oncogene allelic variations in human squamous cell carcinomas of the larynx.
Proto-oncogene restriction fragment length polymorphisms (RFLPs) were investigated in a group of 23 patients with squamous cell carcinomas of the larynx. The frequency of the rare 5 kb c-mos allele was significantly higher than that observed in control groups of patients with colorectal neoplasms or lymphoproliferative disorders. In addition, the 2 patients heterozygous at the c-mos locus (TC-8 and TC-10) were the only 2 of our series of develop multiple malignancies. Also, the 10 kb L-myc allele was remarkably more represented in patients with laryngeal carcinoma when compared to controls. These findings suggest that c-mos and L-myc RFLPs might be helpful in identifying those individuals who are at a higher risk of developing laryngeal carcinomas. Single allele amplification of L-myc, c-myb and c-mos proto-oncogenes, with no concomitant mRNA hyperexpression, were observed in 3 cases. The results obtained seem to rule out a direct pathogenetic role of these proto-oncogenes and suggest that the amplification of other closely linked genes, located on chromosomes 1, 6 and 8, respectively, may be causally associated with the development of these tumors. No allelic deletions at the c-myb locus were observed, whereas a loss of a c-Ha-ras-1 allele was demonstrated in one of the 11 heterozygous patients. Thus, the analysis of polymorphic proto-oncogenes in laryngeal carcinomas allowed us to identify a group of genetic abnormalities (chromosomes 1, 6 and 8 gene amplifications and c-Ha-ras-1 deletions) which may be involved in the development or progression of these tumors.
Division of Experimental Oncology I, Centro di Riferimento Oncologico, Aviano, Italy.
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Dolcetti
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Boiocchi
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015152:Blotting, Northern; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002874:Chromosome Mapping; D015342:DNA Probes; D005784:Gene Amplification; D016258:Genes, mos; D016259:Genes, myc; D011905:Genes, ras; D006689:Hodgkin Disease / Q000235:genetics; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D012150:Polymorphism, Restriction Fragment Length; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes
D015342:DNA Probes; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas