Amplification of 8p11.23 in cancers and the role of amplicon genes

Copy number alterations are widespread in cancer genomes and are part of the genomic instability underlying the pathogenesis of neoplastic diseases. Recurrent copy number alterations of specific chromosomal loci may result in gains of oncogenes or losses of tumor suppressor genes and become entrenched in the genomic framework of certain types of cancers. The locus at chromosome 8p11.23 presents recurrent amplifications most commonly in squamous lung carcinomas, breast cancers, squamous esophageal carcinomas, and urothelial carcinomas. Amplification is rare in other cancers. The amplified segment involves several described oncogenes that may promote cancer cell survival and proliferation, as well as less well characterized genes that could also contribute to neoplastic processes. Genes proposed to be “drivers” in 8p11.23 amplifications include ZNF703, FGFR1 and PLPP5. Additional genes in the locus that could be functionally important in neoplastic networks include co-chaperone BAG4, lysine methyltransferase NSD3, ASH2L, a member of another methyltransferase complex, MLL and the mRNA processing and translation regulators LSM1 and EIF4EBP1. In this paper, genes located in the amplified segment of 8p11.23 will be examined for their role in cancer and data arguing for their importance for cancers with the amplification will be presented.