Fractional allele loss data indicate distinct genetic populations in the development of non-small-cell lung cancer

Allelic imbalance or loss of heterozygosity (LOH) has been widely used to assess genetic instability iii tumours. and high LOH on chromosome arms 3p. 9p and 17p has been considered to be a common event in non-small-cell lung cancer (NSCLC). We have investigated allelic imbalance in 45 NSCLCs using 92 microsatellite markers on 3S chromosome arms. LOH of 38% was observed on 3p using nine markers, 58% on 9p using 15 markers and 35% on 17p using five markers. Fractional allele loss (FAL) has been calculated for each tumour (FAL is the number of chromosome arms showing LOH/number of informative chromosome arms) and a median FaL value of 0.09 was obtained in the 35 NSCLCs studied. The LOH data were examined an the basis of FAL scores: low FAL (LFAL) (0.00 - 0.04), medium FAL (MFAL) (0.05 - 0.13) and high FAL (HFAL) (0.14 - 0.45) based symmetrically around the median FAL value of 0.09. Tumours with HFAL values showed a very clear polarisation of the LOW data oil chromosome arms 3p, 9p and 17p. such that 80% showed loss on 3p, 80% on 9p and 73% on 17p, These incidences of LOH were significantly higher than would be expected, since overall genetic instability in these HFAL tumours ranged from 14% to 45% LOH. Nine of the 14 patients in the LFAL group were found to have no LOH on 3p, 9p or 17p, but five of these had LOH at other sites: i.e. LON on 5p 5q, 8p, 13q, 16q and 19q. These results indicate that LFAL patients form a new subset of NSCLC tumours with distinct molecular-initating events. and may represent a discrete genetic population.