Carcinogenesis, Vol. 20, No. 12, 2219-2228,
December 1999
© 1999 Oxford University Press
Cancer Biology |
Fractional allele loss indicates distinct genetic populations in the development of squamous cell carcinoma of the head and neck (SCCHN)
1 Molecular Genetics and Oncology Group, Clinical Dental Sciences, The University of Liverpool, Liverpool L69 3BX,
2 Department of Medicine, The University of Liverpool, Liverpool L69 3GA, UK,
3 Deparment of Biochemistry, Faculty of Science, Annamalai University, Tamilnadu, India,
4 Department of Otorhinolaryngology, The University of Liverpool, Liverpool L69 3BX, UK,
5 Maxillofacial Unit, Fazakerley Hospital, Liverpool,
6 Department of Pathology, The University of Liverpool, Liverpool L69 3BX and
7 The Roy Castle International Centre for Lung Cancer Research, Liverpool L3 9TA, UK
Loss of heterozygosity (LOH) had been widely used to assess genetic instability in tumours and a high LOH on chromosome arms 3p, 9p and 17p has been considered to be a common event in squamous cell carcinoma of the head and neck (SCCHN). We have investigated LOH in 52 SCCHN using a range of microsatellite markers. LOH was observed in 69% of individuals on 17p using seven markers, in 64% of individuals on 3p using 17 markers and in 61% of individuals on 9p using 11 markers. Fractional allele loss (FAL) has been calculated for each tumour (FAL is the number of chromosomal arms showing LOH divided 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 the 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 indicate that LFAL patients form a subset of SCCHN tumours with distinct molecular initiating events which may represent a discrete genetic population.
Abbreviations: FAL, fractional allele loss; HGI, high genomic instability; LGI, low genomic instability; LOH, loss of heterozygosity; NSCLC, non-small cell lung cancer; SCCHN, squamous cell carcinoma of the head and neck; SSCP, single-strand conformation polymorphism; TSGs, tumour suppressor genes.
8 To whom correspondence should be addressed Email: j.k.field{at}liv.ac.uk
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