Oncogene Amplification in Squamous Cell Carcinoma of the Oral Cavity

Abstract

We have determined the prevalence of amplification of c‐myc, N‐myc, L‐myc, H‐ras, Ki‐ras, and N‐ras oncogenes in 23 cases of squamous cell carcinoma of the oral cavity, using Southern hybridization analysis of DNA extracted from the primary tumor tissues. Nick‐translated oncogene probes and oncogene inserts labeled to high specific activities were used. We observed a 5‐ to 10‐fold amplification of one or more of c‐myc, N‐myc, Ki‐ras and N‐ras oncogenes in 56% of the tumor tissue samples, with these oncogenes not being amplified in the peripheral blood cells of the same patients, L‐myc and H‐ras were not amplified in any of our samples. The oncogene amplifications seemed to be associated with advanced stages of squamous cell carcinomas, with the ras and myc family oncogenes being amplified in stages 3 and 4. Hybridization with N‐myc detected an additional 2.3 kb EcoRI fragment, along with the normal 2.1 kb fragment. Our data also demonstrated amplification of multiple oncogenes in the same tumor tissue sample. About 60% of the samples with amplified oncogenes showed simultaneous amplification of 2 or more oncogenes. The results showing different oncogene amplifications in similar tumors, as well as multiple oncogene amplifications in the same tumor, suggest that these oncogenes may be alternatively or simultaneously activated in oral carcinogenesis.

Characterization of transformation related genes in oral cancer cells

“…This in vitro carcinogenesis model, along with the ability to grow NHOK in cell culture, provides an ideal system to study the alterations in gene expression that accompany cancer progression in humans. Although several genes have been reported to be mutated or di erentially expressed in oral cancers (Tadokoro et al, 1989;Saranath et al, 1989;Kannan et al, 1994a,b), a much larger number of genes are likely to be involved in the transformation of oral epithelial cells.…”

Restriction fragment length polymorphism of the L-myc gene in oral cancer patients

“…Hybridisation, washing and autoradiography were carried out as previously described (Saranath et al, 1989). Hind (Table I).…”

“…Recent studies from our laboratory have demonstrated the involvement of oncogenes in squamous cell carcinoma of the oral cavity, via amplification of myc and ras family genes (Saranath et al, 1989). A 5-10-fold amplification of Ki-ras was reported in 17% and 30%, respectively, of the oral cancer samples investigated.…”

Elevated P53 expression correlates with a history of heavy smoking in squamous cell carcinoma of the head and neck

“…Chiba et al (1990) We have previously demonstrated that there is elevated expression of several oncogenes, (Ha-ras, Ki-ras, c-erbB-2 and c-myc) in the development of squamous cell carcinoma of the head and neck (Field et al, 1986(Field et al, , 1987(Field et al, , 1989(Field et al, , 1990Field, 1991). We have reported a correlation between elevated c-myc oncoprotein expression and poor prognosis (Field et al, 1989), but as yet there is no published evidence to demonstrate that amplification or point mutations of oncogenes are associated with the clinical outcome of these patients (Saranath, 1989;Rumsby et al, 1989;Sheng et al, 1990;Field et al, unpublished). Parada et al (1984) have previously reported co-operation between p53 tumour antigen and ras in cellular transformation.…”