Amplification of Chromosome 8 Genes in Lung Cancer

Abstract

Chromosomal alterations are frequent events in lung carcinogenesis and usually display regions of focal amplification containing several overexpressed oncogenes. Although gains and losses of chromosomal loci have been reported copy number changes of the individual genes have not been analyzed in lung cancer. In this study 22 genes were analyzed by MLPA in tumors and matched normal tissue samples from 82 patients with non-small cell lung cancer. Gene amplifications were observed in 84% of the samples. Chromosome 8 was found to harbor the most frequent copy number alterations. The most frequently amplified genes were ZNF703, PRDM14 and MYC on chromosome 8 and the BIRC5 gene on chromosome 17. The frequency of deletions were much lower and the most frequently deleted gene was ADAM9. Amplification of the ZNF703, PRDM14 and MYC genes were highly correlated suggesting that the genes displaying high copy number changes on chromosome 8 collaborate during lung carcinogenesis.

Copy number profiling of tumor suppressor genes in head and neck cancer

“…Moreover, similar frequencies of copy number changes and a highly significant correlation between the CDKN2A and CDKN2B genes in our cohort support the fact that different tumor suppressor genes in this region may cooperate in HNSCC . This observation is also in line with our previous findings revealing collaboration of different amplicons in lung cancer . An interesting fact is the report indicating that 9p deletions involving the CDKN2A locus may sometimes occur against a background of copy number gains .…”

“…Resolution of conventional comparative genomic hybridization (CGH) is not sufficient for the precise identification of the molecular changes on the gene level . Multiplex ligation‐dependent probe amplification (MLPA) is a molecular technique that allows targeting and analysis of up to 50 different chromosomal sequences as well as intragenic rearrangements in a single reaction . The power of MLPA has not been evaluated for the analysis of gene copy numbers in head and neck cancer.…”

ZNF703 Overexpression may act as an oncogene in non‐small cell lung cancer

“…It has also been shown that ZNF703 is overexpressed in 15% of breast cancers that harbor 8p12 amplifications . In our previous study we detected ZNF703 amplification in 43.2% of the NSCLC tumor tissues . Therefore, in this study we investigated the expression of ZNF703 to identify whether overexpression of ZNF703 occurs as a result of amplification in NSCLC.…”

ZNF703 is an important player in head and neck cancer

“…As a result of chromosomal breaks and rearrangements, oncogenes and tumour suppressor genes which are found at the 8p11‐12 region contribute to tumour development and oncogenesis . The gene coding for the ZNF703 transcription factor is one of the frequently amplified genes in this region . ZNF703 regulates expression of multiple genes involved in transcription modulation, adhesion, motility, differention, stem cell renewal and invasion …”