Consistent with these multiple and complex roles, both overexpression of POLK (associated with advanced disease stages and shorter survival in patients with glioma[47] and non-small cell lung carcinomas[48]) and under-expression of POLK (frequently observed in colorectal, lung, stomach, and breast cancers[29,35,49,50]) have been documented to lead to genetic instability. This evidence concerns the gene POLK and central nervous system cancer.