Original Paper Expression Analysis of Genes at 3q26-q27 Involved in Frequent Ampli®cation in Squamous Cell Lung Carcinoma A. Ra Âcz, 1 N. Brass, 1 D. Heckel, 1 S. Pahl, 2 K. Remberger 2 and E. Meese 1 1 Department of Human Genetics, Building 60; and 2 Department of Pathology, Medical School, University of Saarland, D-66421 Homburg/Saar, Germany Gene ampli®cations are known to occur frequently in lung cancer. Recently, we identi®ed gene ampli®cations at 3q26 in squamous cell lung carcinoma (SCC) using reverse chromosome painting. Here, our aim was to analyse the expression of genes which map within the ampli®ed chromosomal region. The genes which were selected for their known function and their potential involvement in tumour development included the genes for ribosomal protein L22 (RPL22), butyrylcholinesterase (BCHE), glucose transporter 2 (SLC2A2), transferrin receptor (TFRC), thrombopoietin (THPO) and the phosphatidylinositol-3 kinase catalytic alpha polypeptide (PIK3CA). While ®ve genes were expressed in the majority of the 17 samples of SCC, the gene for the glucose transporter 2 (SLC2A2) was expressed in only three cases, excluding SLC2A2 as the target gene of the ampli®cation unit. For a subset of tumours, we determined the ampli®cation status of the six genes. The TFRC, PIK3CA, BCHE, THPO and SLC2A2 genes were ampli®ed in several cases, whereas the RPL22 gene was ampli®ed in only one case. The combined ampli®cation and expression data of this and our previous studies indicate that the ampli®ed region at 3q26 contains several genes that are transcribed in SCC, providing the possibility that several ampli®ed and functionally important genes at 3q26 may be involved in the pathogenesis of SCC. # 1999 Elsevier Science Ltd. All rights reserved. Key words: squamous cell lung carcinoma (SCC), gene ampli®cation, gene expression, chromosomal band 3q26-q27 Eur J Cancer, Vol. 35, No. 4, pp. 641±646, 1999 INTRODUCTION Various types of human cancer are characterised by gene ampli®cation including neu in breast cancer, EGFR and Gas41 in glioma and N-myc in neuroblastoma [1, 2]. Recently developed approaches including comparative genomic hybri- disation (CGH) and microdissection-mediated cDNA cap- ture greatly facilitated the identi®cation and cloning of ampli®ed DNA domains which appear to be even more fre- quent in human cancers than previously predicted [3, 4]. The detection of gene ampli®cation in tumour cells has been shown to be of prognostic signi®cance [5, 6]. Most notably, clinical trials are underway demonstrating that the decision for chemotherapeutic intervention in neuroblastoma can be based solely on N-myc ampli®cation [7]. Recently, cytogenetic studies showed double minutes as cytogenetic manifestations of DNA ampli®cations in non- small cell lung cancer which accounts for more than 75% of all lung cancers [8]. CGH revealed 22 diVerent ampli®ed domains in small cell lung carcinoma [9]. Southern-blot analysis indicated several ampli®ed oncogenes in lung carci- noma including c-myc and K-ras2 [10, 11]. While the afore- mentioned gene ampli®cations were relatively rare in lung cancers, we recently reported ampli®cations at chromosome band 3q26 in approximately 40% of squamous cell lung car- cinomas (SCC) [12]. The ®rst evidence for frequent ampli®- cation at 3q26 in SCC stems from reverse chromosome painting [13]. Subsequent studies revealed frequent ampli®- cation of the butyrylcholinesterase (BCHE) and glucose transporter 2 (SLC2A2) genes, both of which are localised within the ampli®ed domain at 3q26 [12]. Here, we further characterised the ampli®ed domain at 3q26 in SCC. Speci®cally, we analysed the expression of European Journal of Cancer, Vol. 35, No. 4, pp. 641±646, 1999 # 1999 Elsevier Science Ltd. All rights reserved Pergamon Printed in Great Britain PII: S0959-8049(98)00419-5 0959-8049/99/$ - see front matter 641 Correspondence to E. Meese, e-mail: hgemee@med-rz.uni-sb.de Received 28 Apr. 1998; revised 30 Oct. 1998; accepted 2 Nov. 1998.