Pergamon PII: S0964-1955 (97)00031-6 Oral Oncology, Vol. 33, No. 6, pp. 414418, 1997 (C 1997 Elsevier Science Ltd. All rights reserved Printed in Great Britain 1368-8375/97 $17.00+0.00 Assessment of Chromosomal Gains and Losses in Oral Squamous Cell Carcinoma by Comparative Genomic Hybridisation M. A. J. A. Hermsen, 1. H. Joenje, 1 F. Arwert, 1 B. J. M. Braakhuis, 2 J. P. A. Baak, 3 A. Westerveld 4 and R. Slater 4. 1Department of Human Genetics, Free University; 2Department of Otorhinolaryngology/Head and Neck Surgery; 3Department of Pathology, Free University Hospital; and 4Institute of Human Genetics, University of Amsterdam, Amsterdam, The Netherlands Cytogenetic studies have demonstrated that oral squamous cell carcinomas (OSCCs) are usually charactefised by complex karyotypes with many marker chromosomes. We analysed the genetic changes of six OSCC cell cultures by comparative genomic hybridisation (CGH). The CGH technique provides info~iiiation on chromosomal gains and losses of the whole tumour genome in a single experiment and can therefore identify regions that harbour putative tumour suppressor genes (in the case of loss of chromosomal material) or oncogenes (in the case of gain or amplification of chromo- somal material). Recurrent losses were detected at chromosome arms Xp and 3p (four cases). Gains consistently occurred at chromosome arms 8q and 9q (four cases) and at lq, 3q, 5p, 7p, and 9p (three cases). The same six tumour cultures have previously been analysed by classical karyotyping. An important discrepancy between the two techniques was the number of losses detected: 55 with karyo- typing versus 26 with CGH. On the basis of the cytogenetic complexity of these tumours and on FISH experiments that confirmed the CGH results, we conclude that genetic changes, particularly losses, can be more reliably detected by CGH analysis. © 1997 Elsevier Science Ltd. All fights reserved. Key words: oral carcinoma, comparative genomic hybridisation, cytogenetics, fluorescence in situ hybridisation Oral Oncology, Vol. 33, No. 6, pp. 414-418, 1997 INTRODUCTION The multistep genetic pathway of oral squamous cell carci- noma (OSCC) development is still poorly understood. This is partly because OSCCs are among the most cytogenetically complex of all solid tumours; nearly all chromosomes have been reported to be involved in both numerical and structural aberrations. In order to identify which genetic changes are critically involved in the process of tumour initiation and progression, the combined data of many studies are needed. The most frequently reported non-random genetic changes are losses at 3p, 8p, 9p, 18q, and gains at 3q, 5p, 7p and 8q [1-5]. A limited number of chromosomal bands appear to be *Present address: Department of Pathology, University Hospital, Vrije Universteit, Amsterdam, The Netherlands. tPresent address: Department of Clinical Genetics and Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands. Correspondence to H. Joenje. Received 3 Jan. 1997; provisionally accepted 3 Feb. 1997; revised manuscript received 10 Apr. 1997. frequently involved in breakpoints, such as lp13, lp22, 3pl 3, and the centromeric regions of all chromosomes, which result in gains and losses of whole chromosome arms [4-6]. Structural variation in band 1 lq13 is often associated with amplification of the oncogenes FGF3, FGF4, cyclin D1 and EMS1 [7, 8]. Amplification of these genes has been reported to be associated to disease progression or clinical outcome [9, 101. In an earlier study we have shown that centromeric breaks and fusions play an important role in contributing to chro- mosomal losses and gains in these turnours [5]. These data suggest that consistent gains and losses, rather than band- specific breakpoints may be a crucial type of event leading to tumour development in OSCC. In addition, unidentifiable marker chromosomes are commonly found in OSCC. It is therefore difficult to obtain an accurate estimate of the genetic changes using only cytogenetic techniques. Recently a new technique has been developed, compara- tive genomic hybridisation (CGH) [11,12], with which chromosomal gains and losses can be more rapidly investigated 414