TY - JOUR
T1 - Landscape of CDKN1B mutations in luminal breast cancer and other Hormone-Driven Human Tumors
AU - Cusan, Martina
AU - Mungo, Giorgia
AU - Zompit, Mara De Marco
AU - Segatto, Ilenia
AU - Belletti, Barbara
AU - Baldassarre, Gustavo
PY - 2018/7/17
Y1 - 2018/7/17
N2 - The CDKN1B gene encodes for the p27Kip1 protein, firstly characterized as a cyclin dependent kinase (CDK)-inhibitor. Germline CDKN1B 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 CDKN1B 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, CDKN1B is mutated in a significant percentage of analyzed samples. Recent works have demonstrated that CDKN1B 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 CDKN1B 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 CDKN1B in human cancers, interpreting the possible impact of these mutations on p27Kip1 protein function and tumor onset and progression.
AB - The CDKN1B gene encodes for the p27Kip1 protein, firstly characterized as a cyclin dependent kinase (CDK)-inhibitor. Germline CDKN1B 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 CDKN1B 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, CDKN1B is mutated in a significant percentage of analyzed samples. Recent works have demonstrated that CDKN1B 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 CDKN1B 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 CDKN1B in human cancers, interpreting the possible impact of these mutations on p27Kip1 protein function and tumor onset and progression.
KW - CDKN1B gene
KW - Driver mutation
KW - Germinal mutation
KW - Intrinsically disordered protein/region
KW - p27 protein
KW - Passenger mutation
KW - Somatic mutation
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U2 - 10.3389/fendo.2018.00393
DO - 10.3389/fendo.2018.00393
M3 - Review article
AN - SCOPUS:85050116651
VL - 9
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
SN - 1664-2392
IS - JUL
M1 - 393
ER -