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Thirteen laryngeal squamous cell carcinoma cell lines were recently studied by array comparative genomic hybridization (array-CGH) in order to identify recurrent DNA copy number alterations in the tumor genome. A highly amplified region 22q11.2 was found in two of the thirteen cell lines. Two established oncogenes CRKL and MAPK1 are localized in this region, but only CRKL was amplified in both cell lines. Therefore, to check if amplification of either CRKL or MAPK1 genes may be important in the pathogenesis of laryngeal squamous cell carcinoma, the DNA copy number and mRNA expression were measured in a cohort of 17 LSCC cell lines by quantitative real-time PCR (qPCR). For the CRKL gene gains of the copy number were found in 3/17 cell lines, while overexpression was found in 6/17 cell lines. Gains in the copy number for the MAPK1 gene were found in 1/17 cell lines, but overexpression was not detected in any cell line. A highly significant correlation between DNA copy number and expression for CRKL gene, but not for MAPK1 gene was established using the Pearson test. Thereafter, 46 primary samples of laryngeal cancer were tested by qPCR to check for possible gains in copy number of the CRKL gene. Gains were found in 3/46 cases. These results suggest that CRKL, but not MAPK1 is the target oncogene of the rare but recurrent amplification at 22q11.2 in laryngeal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Cell lines provide a good model for studies on molecular and cellular events accompanying neoplastic transformation and cancer progression. The data in recent literature suggest an occurrence of repetitive chromosome aberrations that can be linked with particular stages of cancer. Ten cell lines derived from squamous cell carcinoma of the larynx at the University of Turku were karyotyped. The studied cell lines represented a variety of primary locations of the tumors, TNM staging and histological grading. Karyotyping was done by the classical cytogenetic technique with the application of GTG, QFQ and other banding techniques; some complex aberrations were analyzed by the FISH technique. The results document several numerical and structural aberrations. Attention was focused on the monosomy of chromosomes 13, 17 and 18, frequent deletions of the Y chromosome. Structural aberrations were frequently seen at chromosomes 1, 3, 4, 7, 8, 9 and 11, mostly as deletions (usually deletions of a whole arm), translocations, isochromosomes, duplications and marker chromosomes. The study is in progress and aims to find a correlation between particular aberrations and disease staging. At present, two observations seem to be firm: the amplification of the 11q13 region appeared in tumors with a short survival. However, the primary location of the tumor should be taken into account when considering 11q13 as a prognostic marker. The same is applicable for del(9p), which indicates an early stage of disease. Besides the frequent chromosome aberrations, attention should be paid to marker chromosomes that are potentially specific for laryngeal cancer. [ABSTRACT FROM AUTHOR]