There is abundant evidence published associating the CDKN1B gene with multiple endocrine neoplasia type 4 (MEN4) since the gene-disease relationship was first proposed by Pellegata et al. (2006). Germline CDKN1B mutations are rare, but nine case level studies have been performed so far with MEN4 patients that have variants in the CDKN1B gene. CDKN1B is a negative regulator of cell cycle progression, and its loss is associated with disease progression and unfavorable outcome in many cancer types. CDKN1B show very low nuclear expression in parathyroid adenoma cells and endocrine pancreatic tumor from MEN4 patients. p27wt inhibits the growth of p27-negative GH3 cells in clonogenic assay while p27W76X does not. Mouse and Rat models have been established to show the development of multiple endocrine tumors with CDKN1B deficiency. All of these types of evidence are consistent with a definitive relationship between the CDKN1B gene and multiple endocrine neoplasia type 4 (MEN4).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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