Cancer

Giant cell glioblastomas (GC); polyploidy; neuroblastomas (NB), susceptibility

AurB may be a tumour requiring protein (TRP). AurB is overexpressed in colorectal cancers and other tumour cell lines, which was thought to lead to multinuclearity, increased ploidy, and a predisposition to cancer. Through its dominant-negative effect on cytokinesis, disruptive regulation of its expression is potentially responsible for the perturbing the chromosomal integrity in cancer cells. K106R mutation leads to loss of phosphotransferase activity, and severely impairs mitosis. Its low rate of mutation and down-regulation in human cancers supports it identification as a tumour-requiring protein, and as a target for cancer drug development.
 

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Barrett's esophagus epithelial metaplasia (%CFC= +60, p<0.064); Bladder carcinomas (%CFC= +93, p<0.028); Breast sporadic basal-like cancer (BLC) (%CFC= +52, p<0.0005); Cervical cancer (%CFC= -52, p<0.0001); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= -76, p<0.0002); Head and neck squamous cell carcinomas (HNSCC) (%CFC= +48, p<0.0002); Lung adenocarcinomas (%CFC= +137, p<0.0008); Prostate cancer - metastatic (%CFC= +73, p<0.0001); Prostate cancer - primary (%CFC= +305, p<0.0002); Skin squamous cell carcinomas (%CFC= +117, p<0.027); and Vulvar intraepithelial neoplasia (%CFC= +161, p<0.0005). The COSMIC website notes an up-regulated expression score for AurB in diverse human cancers of 861, which is 1.9-fold of the average score of 462 for the human protein kinases. In particular, in 266 ovarian cancer specimens analyzed 86% showed AurB over-expression. The down-regulated expression score of 3 for this protein kinase in human cancers was 0.1-fold of the average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.

Percent mutation rates per 100 amino acids length in human cancers: 0.07 % in 25543 diverse cancer specimens. This rate is only -9 % lower and is very similar to the average rate of 0.075 % calculated for human protein kinases in general.

Highest percent mutation rates per 100 amino acids length in human cancers: 0.27 % in 1093 large intestine cancers tested.

Most frequent mutations with the number of reports indicated in brackets: R284H (4)

No deletions, insertions or complex mutations are noted on the COSMIC website.