Distinct patterns of genetic alterations in adenocarcinoma and squamous cell carcinoma of the lung S.M.-H. Sy a , N. Wong a, *, T.-W. Lee b , G. Tse c , T.S.-K. Mok a , B. Fan a , E. Pang a , P.J. Johnson d , A. Yim b a Department of Clinical Oncology, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, SAR Hong Kong, China b Department of Surgery, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, SAR Hong Kong, China c DepartmentofAnatomicalandCellularPathology,SirY.K.PaoCentreforCancer,TheChineseUniversityofHongKong,Shatin,SARHongKong,China d Department of Oncology and Translational Research, University of Birmingham, UK Received 28 October 2003; received in revised form 12 January 2004; accepted 15 January 2004 Abstract Squamous cell carcinoma (SqC) and adenocarcinoma (AdC) are the two most common subtypes of non-small cell lung cancer (NSCLC). Cumulative information suggests that the SqC and AdC subtypes progress through different carcinogenic pathways, but the genetic aberrations promoting such differences remain unclear. Here we have assessed the overall genomic imbalances and structural abnormalities in SqC and AdC . By parallel analyses with comparative genomic hybridisation (CGH) on tumorous lung tissues and spectral karyotyping (SKY) on short-term cultured primary tumours, genome-wide characterisation was carried out on 69 NSCLC (35 SqC, 34 AdC). Molecular cytogenetic characterisation indicated common and distinct genetic changes in SqC and AdC. Common events of +1q21-q24, +5p15-p14, and +8q22-q24.1, and 17p13-p12 were found in both groups, although hier- archical clustering simulation on CGH findings depicted +2p13-p11.2, +3q25-q29, +9q13-q34, +12p, +12q12-q15 and +17q21, and 8p in preferential association with SqC pathogenesis (P < 0.05). Corresponding SKY analysis suggested that these changes occur in simple and complex rearrangements, and further indicated the clonal presence of translocation partners leading to chro- mosomal over-representations. These recurring rearrangements involved chromosome pairs of t(1;13), t(1;15), t(7;8), t(8;15), t(8;9), t(2;17) and t(15;20). Of particular interest was the finding that the t(8;12) translocation partner was exclusive to AdC. The com- bined application of SKY and CGH has thus uncovered the genome-wide chromosomal aberrations in NSCLC. Specific chromo- somal imbalances and translocation partners found in SqC and AdC have highlighted regions for further molecular investigation into gene(s) that may hold importance in the carcinogenesis of NSCLC. # 2004 Elsevier Ltd. All rights reserved. Keywords: NSCLC; Comparative genomic hybridisation; Spectral karyotyping 1. Introduction Lungcancerisresponsibleforthehighestcancer-related morbidity and mortality worldwide [1]. Non-small cell lung cancer (NSCLC) comprises approximately 80% of all lung cancers, among which adenocarcinoma (AdC) and squamous cell carcinoma (SqC) are now the two most common histological subtypes. Cigarette smoking continues to be an important aetiological factor, with a clear implication of involvement in over 95% of male cases [2]. A correlation between the incidence of lung cancer in females and smoking habit has also been observed in recent years [3]. Due to the high incidence and mortality rates, much effort has been drawn towards investigating the cause and course of NSCLC. Although classical cytogenetic studies by banding analysis can provide an overall view of structural and numerical abnormalities, the frequent presence of karyotypic complexity has precluded more accurate interpretation. Conversely, molecular char- acterisation by comparative genomic hybridisation (CGH) and allelotyping has shown common over- 0959-8049/$ - see front matter # 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2004.01.012 European Journal of Cancer 40 (2004) 1082–1094 www.ejconline.com * Corresponding author. Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N. T., SAR Hong Kong, China. Tel.: +852-2632-1128; fax: +852- 2648-8842. E-mail address: natwong@cuhk.edu.hk (N. Wong).