DNA amplification on chromosome 6p12 in non small cell lung cancer detected by arbitrarily primed polymerase chain reaction

Gene amplification is clearly an important aspect of tumour growth and deve lopment and has prognostic significance in certain tumours. The identificat ion and genetic characterisation of new areas of amplification in human mal ignancy remains an important goal in understanding the underlying genetic l esions within these tissues. In the present work, arbitrarily primed-PCR (A P-PCR) has been applied to detect and characterise amplified DNA fragments in human non small cell lung cancer (NSCLC). Our results show that gains of genomic sequences occur at high frequency (64% of all genomic changes anal ysed). Moreover, we succeeded in detecting a genomic sequence that is highl y amplified in one of the tumours analysed. The amplification intensity of this DNA fragment was also increased in 29 (45%) of the 65 NSCLC patients f rom our study. The amplified DNA fragment was isolated and identified as a 600 bp sequence mapped to chromosome 6p12. This sequence did not show signi ficant homology with known human DNA sequences. Interestingly, a gene relat ed to cancer processes, the pim-l oncogene, is placed neighbouring to this region on chromosome 6. Survival studies revealed that disease-free interva l of NSCLC patients was shorter in patients bearing the amplified sequence (p = 0.05 by the Breslow test). Our findings suggest that the amplified seq uence located on chromosome 6 might be relevant in the pathogenesis of huma n NSCLC. int. J. Cancer (Pred. Oncol.), 84:344-349, 1999. (C) 1999 Wiley-Li ss, Inc.