Ras mutations in united kingdom examples of oral malignancies are infrequent

Abstract

Point mutations in codons 12, 13 or 61 of the oncogenes Ha-ras, Ki-ras or N-ras have been identified in human malignancies of many types. Using the PCR (polymerase chain reaction) technique for DNA amplification in vitro and stringent probing of the amplified DNA on dot blots with a library of specific oligonucleotides, we have screened for the presence of ras mutations in oral and para-oral malignancies and some associated lesions. The material, from UK patients, consisted of 22 oral squamous-cell carcinomas including 5 neck metastases, 1 oral mucosal dysplasia, 1 proliferative verrucous leukoplakia, 1 antral and 1 tonsillar carcinoma, 1 basal-cell carcinoma, 1 salivary adenocarcinoma, 1 salivary adenoid cystic carcinoma and 1 lung adenocarcinoma metastatic to the gingiva. Genomic DNA was extracted from tissues which were fresh or preserved in liquid nitrogen. Two DNA samples contained point mutations in codon 61 of Ki-ras. One of these mutations was in the lymphocytes infiltrating a retromolar SCC. The other mutation (CAA to CAU; substitution of glutamine by histidine) was in the lung adenocarcinoma metastasis. The absence of ras mutations in the epithelium of primary oral squamous-cell carcinomas is of considerable interest as other work in our Department on Indian cases of oral carcinomas associated with chewing tobacco (quid) revealed that 35% of these had a codon 12, 13 or 61 mutation in Ha-ras. While ras activations arising from point mutations may occur in a high proportion of oral malignancies associated with chewing tobacco (quid), this was not the case in UK oral malignancies, even where tobacco was smoked.

The absence of Harvey ras mutations during development and progression of squamous cell carcinomas of the head and neck

“…We have confirmed and extended the observations of previous investigators (Rumsby et al, 1990;Sheng et al, 1990;Chang et al, 1991) to demonstrate that mutations in the H-ras proto-oncogene are extremely rare in the pathogenesis of H & N SCC in Caucasian patients. Extending the findings of others, we were unable to find H-ras mutations in 11 premalignant or benign lesions and 20 early stage (T1, T2) untreated SCC which were not studied by the earlier investigators.…”

Molecular Biology of Human Oral Cancer

“…A report from India demonstrated that 35% of oral squamous cell carcinomas contained H-ras mutations (Saranath et al, 1991). However, studies from the Western world have shown that H-ras mutations are found in fewer than 5% of head and neck cancers (Rumsby et al, 1990;Sheng et al, 1990;Chang et al, 1991;Hirano et al, 1991). In oral cancer, Kirsten ras (K-ras) has been shown to be activated by a point mutation (Spandidos et al, 1985); thus, it remains activated, but unable to hydrolyze GTP due to an amino acid change resulting from this mutation (Barbacid, 1987).…”

H-Ras mutation modulates the expression of major cell cycle regulatory proteins and disease prognosis in oral carcinoma

“…In oral carcinomas, the frequency of Ras mutation showed great demographic variation. Ras mutation has been reported in 20-35% of the cases from India, [8][9][10] whereas lower frequencies (4%) were reported from the United Kingdom 11 and no mutation was reported from the Unites States. 12 Davies et al 13 revealed activating mutations in the B-Raf kinase gene in greater than 60% of melanomas and a broad range of other cancers.…”