Fractional allele loss indicates distinct genetic populations in the development of squamous cell carcinoma of the head and neck (SCCHN)

Loss of heterozygosity (LOH) had been widely used to assess genetic instabi lity in tumours and a high LOH on chromosome arms 3p, 9p and 17p has been c onsidered to be a common event in squamous cell carcinoma of the head and n eck (SCCHN), We have investigated LOH in 52 SCCHN using a range of microsat ellite markers. LOH was observed in 69% of individuals on 17p using seven m arkers, in 64% of individuals on 3p using 17 markers and in 61% of individu als on 9p using 11 markers. Fractional allele loss (FAL) has been calculate d for each tumour (FAL is the number of chromosomal arms showing LOH divide d by the number of informative chromosomal arms) and a median FAL value of 0.25 was obtained in the 52 SCCHN studied. The LOH data were examined on th e basis of FAL scores: low FAL (LFAL), 0.00-0.19; medium FAL (MFAL), 0.20-0 .32; high FAL (HFAL), 0.33-0.88. HFAL tumours demonstrated a significantly higher LOH on chromosome arms 3p, 9p and 17p, with 94% LOH on 3p, 94% on 9p and 100% on 17p compared with LFAL tumours, Six of the 16 patients in the LFAL group were found to have no LOH on 3p, 9p or 17p and of these four had LOH at other sites, on chromosomes 2p25-p24, 5q21-22, 7pter-p22, 8q13-q22. 1, 11q23.3, 13q32, 17q, 18p11.21, 18q21.31 and 19q12-q13.1. These results i ndicate that LFAL patients form a subset of SCCHN tumours with distinct mol ecular initiating events which may represent a discrete genetic population.