Abstract
Background: Amplification of the locus 8p11.23 has been observed in cancer and genes of this locus, including ZNF703 (Zinc finger protein 703), NSD3 (Nuclear receptor binding SET domain protein 3) and FGFR1 (Fibroblast growth factor receptor 1), have been put forward as dominant oncogenes conferring pathophysiologic benefit in cancers with amplifications. However, there is no consensus on the importance of each of them or any other genes of the amplicon or even a consensus on which genes are part of the amplicon. Methods: Publicly available data were used to characterize the locus amplified at 8p11.23 and derive information on each of the genes and roles as oncogenes. The frequency of the amplifications in the locus was examined in the cBioportal platform, and expression levels of the amplicon genes in amplified cases were derived from genomic studies reported in the platform. Examination of the influence of mRNA expressions of each gene of the locus for Recurrence-free survival in breast cancer was performed using K-M plotter. Results: The 8p11.23 amplicon is present in higher frequency in squamous cell lung carcinomas, breast cancers and bladder carcinomas and is only rarely observed in other cancers. The most frequently amplified genes within the amplicon vary between different types of cancers. In breast cancer, amplified cases are most commonly of the luminal B type. Amplified genes are not always over-expressed and there is a low correlation of amplification with over-expression in amplicon genes with variation between genes. The presence of the amplicon does not influence the aneuploidy score or the tumor mutation burden of breast cancers. Regarding prognosis, the two genes of the amplicon whose mRNA hyper-expression portends adverse relapse-free survival in breast cancer are EIF4EBP1 (Eukaryotic transcription initiation factor 4E binding protein 1) and LSM1 (LSM1 homolog, mRNA degradation associated). Conclusion: Besides the previously proposed genes to play a role as dominant oncogenes in the 8p11.23 cancer amplified locus, other genes may also be important in breast cancer based on the high correlation of their amplification and mRNA expression and adverse prognosis conferred by over-expression, consistent with an oncogenic role.
Highlights
Copy number alterations, both gains and losses, are common molecular lesions in cancer and complement mutations and epigenetic changes in the development of neoplasia [1]
This paper investigates another amplicon at locus 8p11.23, commonly observed in breast cancers, using publicly available genomic data and other freely available resources informing on the amplicon genes and their products and putative clinical significance
The 8p11.23 amplicon or areas close to it at 8p have been previously reported to play an oncogenic role in breast cancer and putative driver oncogenes among the genes located in the amplicon have been proposed
Summary
Both gains and losses, are common molecular lesions in cancer and complement mutations and epigenetic changes in the development of neoplasia [1]. A different amplicon based at locus 11q13 contains the gene CCND1 encoding for cyclin D which is implicated in hormonal therapy resistance in breast cancer and is targeted therapeutically by inhibitors of cyclin-dependent kinases [8] Other genes such as those encoding for Fas-Associated Death Domain (FADD) or for the cytoskeleton scaffold protein cortactin are oncogenes frequently co-amplified with CCND1 at 11q13 or independently in some cases [8]. Conclusion: Besides the previously proposed genes to play a role as dominant oncogenes in the 8p11.23 cancer amplified locus, other genes may be important in breast cancer based on the high correlation of their amplification and mRNA expression and adverse prognosis conferred by over-expression, consistent with an oncogenic role
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