ALLELIC LOSS ON CHROMOSOME 10Q IN HUMAN LUNG-CANCER - ASSOCIATION WITH TUMOR PROGRESSION AND METASTATIC PHENOTYPE

We analysed 78 carcinomas of the lung for allelic losses on chromosome 10q. The tumours were of different stage and grade and comprised 22 s mall-cell lung carcinomas (SCLC), 40 squamous cell carcinomas (SCC), 1 1 adenocarcinomas, four large-cell carcinomas and one carcinoid. They were investigated by six polymorphic markers located between 10q21 and 10qter. We observed a high incidence of loss of heterozygosity (LOH) in SCLC (91%) and metastatic SCC (56%). Non-metastatic SCC showed dele tions in three cases (14%) and no LOH was found in the other types of non-small-cell lung cancer. The statistical analysis indicated that th e presence of LOH correlated significantly with advanced tumour stages in the entire collective and in particular within the SCLC and SCC su bgroups. For SCC, a positive association was found between LOH and met astases formation, while in SCLC the number of non-metastatic tumours was too small for a final conclusion. Whereas SCLC was frequently char acterized by multiple allelic losses, suggesting the deletion of the e ntire chromosomal arm, SCC showed interstitial imbalances. A high inci dence of allelic loss was observed between the markers D10S677 and D10 S1223. The analysis of five informative cases suggested the presence o f two non-overlapping regions between the loci D10S677/D10S1237 and D1 0S1213/D10S1223. In SCLC, we did not find mutations in the putative tu mour-suppressor gene MXI1. The data indicate that LOH on chromosome 10 q is associated with tumour progression in SCC and SCLC. Thus it may b ecome a useful genetic marker in the assessment of the malignant poten tial of these tumour types.