Lasko et al., 1991;Latif et al., 1992;Cunningham et al., 1993;Adamson et al., 1994). A number of oncogenic and tumoursuppressor gene functions have been demonstrated in squamous cell carcinoma of the head and neck (SCCHN) (Field et al., 1989(Field et al., , 1991Field, 1992) To date only two global analyses of the whole genome have been undertaken with the view to determine the fractional allele loss (FAL) of specific tumours and thus provide information concerning the 'genetic burden' of the disease during its progression as measured by clinicopathological parameters and survival data. This type of analysis has been undertaken in colorectal (Vogelstein et al., 1989) and bladder cancers (Knowles et al., 1994), and provides an indication of interacting genetic mechanisms in the development of these diseases. In addition, the results of such detailed allelotypes may aid the interpretation of carcinogenesis and the development of molecular progression models for specific tumours.We have undertaken a very comprehensive allelotype of SCCHN using 145 microsatellite markers in order to identify common regions of allelic imbalance and to analyse the interactions of these regions by calculating the fractional allele loss (FAL) in these tumours. Materias and methods Specimens

Sary Alelic loss on chromosome 17 in 18 Barrett's oesophageal tumours was analysed with 17 polymorphic microsatellite markers. Loss of heterozygosity (LOH) of one or more markers was seen in 72% (13 of 18) tumours on 17p and 56% (10 of 18) on 17q. The highest 17p losses were found at D17S799 (62%, five of eight) and D17S261 (55%, five of nine), while loss at the p53 locus was 31% (5 of 16). The highest loss on 17q was found at the TCF-2 (17q11.2-q12) locus with 66% (8 of 12) LOH. TCF-2 was the only marker lost in two of the tumour samples; furthermore, TCF-2 was lost in four other tumours which retained heterozygosity at the markers on either side of it, D17S261 and D17S740. Six markers were used to assess LOH at 17q 1.2-q12, and five of eight of the tumour specimens which had LOH at TCF-2 had no other loss on 17q. No statistically significant correlations were found between loss on 17q or 17p and any clinicopathological parameters. We propose from these data that the 17qll. (Cameron and Lomboy, 1992). During the last two decades the incidence of adenocarcinoma of the oesophagus has increased at a rate exceeding that of any other cancer, with an incidence of 500 cancers per 100 000 patients with Barrett's metaplasia per year (Haggitt, 1992

Summary Allelic imbalance or loss of heterozygosity (LOH) has been widely used to assess genetic instability in 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 38 chromosome arms. LOH of 38% was observed on 3p using nine markers, 58% on 9p using 15 markers and 38% on 17p using five markers. Fractional allele loss (FAL) Keywords: non-small-cell lung cancer; loss of heterozygosity; fractional allele loss; distinct genetic population Allelic imbalance or loss of heterozygosity (LOH) has been widely used to assess genetic instability in tumour tissues. The technique has been used primarily to identify regions on specific chromosomes that could contain putative tumoursuppressor genes, but may also be used to produce a measure of accumulated genetic damage within the genome of each tumour. A number of such allelotype analyses have been undertaken in lung and in head and neck cancers (Tsuchiya et al., 1992;Sato et al., 1994;Ah-See et al., 1994;Nawroz et al.,1994; Field et al., 1995), the largest of which has been on squamous cell carcinoma of the head and neck (SCCHN) and involved the use of 145 microsatellite markers (Field et al., 1995). In this study fractional allele loss (FAL) was calculated for all tumours for which data on nine or more chromosomal arms were available, and the median value was found to be 0.22 (FAL was al., 1989). A large allelotype of non-smallcell lung cancers (NSCLCs) using 92 markers has also been undertaken by this group and has found a median FAL value of 0.09 (Neville et al., 1996). Long-term follow-up for this group of NSCLC patients is as yet unavailable, thus no statistical association has been sought between FAL and survival.The presence and role of allelic imbalance on the short arms of chromosomes 3, 9 and 17 in NSCLC has received a Correspondence: JK Field Received 6 March 1996; revised 21 May 1996; accepted 12 July 1996 great deal of attention and it has been argued that these events are associated with the early stages of pathogenesis of these tumours (Sundaresan et al., 1992;Hung et al., 1995;Gazdar et al., 1994; Kishimoto et al., 1995a,b;Thiberville et al., 1995). In these studies, the investigators studied a small number of dysplastic and neoplastic tissues from the same patient in great detail by performing microdissection of the specimens. All of the six paired dysplastic and tumour tissue specimens investigated by Sundaresan et al. (1992) showed allelic imbalance on 3p and, similarly, Hung et al. (1995) found that six of the seven patients examined with paired preneoplastic and neoplastic lesions showed loss on 3p. Kishimoto et al. (1995b) Table I). After resection, the tumours were taken fresh from the theatre, snap frozen in liquid nitrogen and each subjected to frozen section histological examination.

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