CORRELATION OF LOSS OF HETEROZYGOSITY AT 11P WITH TUMOR PROGRESSION AND SURVIVAL IN NONSMALL CELL LUNG-CANCER

Loss of heterozygosity (LOH) affecting loci at 11p13 and 11p15 occurs in childhood and adult carcinomas, including non-small cell lung cancer (NSCLC). In NSCLC, the highest reported frequency of LOH was 72% at the 11p13 catalase (CAT) locus. As this locus is centromeric to the Wilms' tumour (WTI) focus, possible involvement of WTI in the pathogenesis of NSCLC was considered. We thus examined 101 cases of NSCLC for LOH at the WTI and five other polymorphic loci along I I p. At 11p13, the frequencies of LOH were 20% (9/46) at the FSHB locus, 9% (5/53) at the WTI locus, and [15% (6/41) at the CAT locus. The shortest region of overlap (SRO) at 11p13 was mapped centromeric to, but excluding, the WTI locus. Only adenocarcinomas showed LOH in this region. At 11p15, LOH affected 23% (18/77) of informative cases, with the highest frequency of 36% at the insulin (INS) locus. The SRO at 11p15 was mapped telomeric to the RRMI locus. A third region, at 11p13-15 between WTI and RRMI, was also affected by LOH. LOH at I Ip correlated significantly with advanced T stage and nodal involvement in NSCLC tumours. In the squamous cell carcinoma subtype, LOH along I Ip also correlated with nodal involvement. Furthermore, squamous tumours with LOH involving 11p13 loci had significantly worse survival than those without LOH. These data suggest that tumor suppressor gene(s) on I Ip affect the progression of NSCLC, particularly squamous cell carcinomas. (C) 1994 Wiley-Liss, Inc.