Cancer

Thyroid lymphomas; Male germ cell tumours

CDK1 appears to be a tumour requiring protein (TRP). Gain-of-function mutations in the CDK1 gene have been linked to several forms of cancer, indicating an oncogenic role for the CDK1 protein. Cells transformed with the oncogene MYC undergo apoptosis when treated with small-molecule CDK1 inhibitors. CDK1-inhibitor treatment of MYC-dependent lymphoma and hepatoblastoma cells isolated from mice resulted in decreased tumour growth and prolonged cell survival. In addition, the elevated expression of CDK1 has been reported as a diagnostic marker for cancer progression in esophageal adenocarcinoma, potentially reflecting the role of the CDK1 protein in tumorigenesis. In addition, loss of the normal regulatory mechanisms of CDK1 activity in LZTS1-null mice was observed to predispose the mice to both spontaneous and carcinogen-induced cancer development, indicating that aberrant CDK1 expression functions to promote cancer formation. Furthermore, CDK1 expression can be used as a prognostic indicator for early breast cancer. For example, breast cancer tumours with high expression of CDK1 are correlated with a significantly lower 5-year patient survival rate (66. 9%) than tumours that have low levels of CDK1 expression (84. 2%).
 

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: 0.05 % in 23713 diverse cancer specimens. This rate is only -32 % lower than 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: 2.07 % in 1184 large intestine cancers tested; 1.31 % in 589 stomach cancers tested; 1.04 % in 805 skin cancers tested; 0.95 % in 602 endometrium cancers tested; 0.78 % in 904 ovary cancers tested; 0.74 % in 500 urinary tract cancers tested; 0.6 % in 1942 lung cancers tested; 0.41 % in 816 prostate cancers tested; 0.34 % in 1467 breast cancers tested; 0.27 % in 1226 kidney cancers tested.

Most frequent mutations with the number of reports indicated in brackets: R257Q (3).

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