[Search for the tumor-suppressor gene(s) on chromosome 5q, which may play an important role for the progression of lung cancer].
Although the initial chemo-radiotherapy is relatively effective, lung cancer, especially small cell lung cancer (SCLC) usually becomes resistant for the therapy and gets higher grade of the malignant phenotype. The common genetic abnormalities, such as 3p deletion and mutational inactivation of p53 and Rb gene, have been well known. However, these abnormalities seem to be involved in the development of lung cancer because they could be detected at the early stage or even in the preneoplastic lesion. By means of loss of heterozygosity (LOH), we have determined two regions which are frequently lost in advanced lung cancer, 5q21 and 5q33-35. In previous reports, the low frequency of 5q loss in lung cancer has been shown in masses obtained at early but not advanced stages. Furthermore, we have found that one SCLC case showed a 5q deletion only in metastatic site but not in the primary lesion. These findings suggest that the inactivation of putative tumor suppressor gene(s) on 5q may play an important role for the progression of lung cancer. In 5q21 area, commonly deleted region was estimated to be 3 Mb around APC gene. This region was covered with several YAC clones and some cosmid contigs were constructed from these YAC clones. Two kinds of transcriptional units have been isolated from these contigs by exon-trapping, cross-species hybridization or northern blotting, so far. Since these cDNAs do not show significant homology with any known gene, their function cannot be estimated. We are trying to isolate full length cDNAs and to determine the functional and structural abnormalities in lung cancer at present.
Hosoe
S
S
Department of Medicine III, Osaka University Medical School.
D018288:Carcinoma, Small Cell / Q000235:genetics; D002895:Chromosomes, Human, Pair 5; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*