No 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.

A battery of audiological and vestibular function tests have been performed in 72 cases of confirmed hypothyroidism. The severity of hypothyroidism was graded as mild, moderate or severe depending upon serum protein-bound iodine estimation. The incidence of hearing impairment, tinnitus and vertigo was correlated with the severity of the disease process. The site of lesion causing sensorineural hearing impairment in 25 cases was pinpointed audiologically.

One of the most serious complications of Paget's disease is a significant increase in the incidence of osteosarcoma.Approximately 1% of Paget's patients develop osteosarcoma, an increase in risk that is several thousand-fold higher than the general population. This risk contributes significantly to the mortality and morbidity of Paget's disease patients. We examined several cases of pagetic and sporadic osteosarcoma for tumor-specific loss of constitutional heterozygosity (Lo@ on chromosome l8q. Our analysis found that both pagetic and sporadic osteosarcoma tumors showed LoH for all or part of the distal portion of chromosome 18q. The pattern of LoH in both types of tumors identified a region between loci D18S60 and D18S42 that must contain the putative tumor suppressor locus.