Landscape of CDKN1B Mutations in Luminal Breast Cancer and Other Hormone-Driven Human Tumors.

The gene encodes for the p27 protein, firstly characterized as a cyclin dependent kinase (CDK)-inhibitor. Germline pathogenic variants have been described in hereditary tumors, such as multiple endocrine neoplasia (MEN)-like syndromes and familial prostate cancer. Despite its central role in tumor progression, for a long time it has been proposed that was very rarely somatically mutated in human cancer and that its expression levels were almost exclusively regulated at post-transcriptional level. Yet, the advent of massive parallel sequencing has partially subverted this general understanding demonstrating that, at least in some types of cancer, is mutated in a significant percentage of analyzed samples. Recent works have demonstrated that can be genetically inactivated and this occurs particularly in sporadic luminal breast cancer, prostate cancer and small intestine neuroendocrine tumors. However, a clear picture of the extent and significance of mutations in human malignances is still lacking. To fill this gap, we interrogated the COSMIC, ICGC, cBioPortal, and TRANSFAC data portals and current literature in PubMed, and reviewed the mutational spectrum of in human cancers, interpreting the possible impact of these mutations on p27 protein function and tumor onset and progression.