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ContextGermline mutations in the MEN1 gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome, but in up to 20-25% of clinical MEN1 cases, no MEN1 mutations can be found. Recently, a germline mutation in the CDKN1B gene, encoding p27(Kip1), was reported in one suspected MEN1 family with two acromegalic patients.ObjectiveOur objective was to evaluate the role of CDKN1B/p27(Kip1) in human tumor predisposition in patients clinically suspected of MEN1 but testing negative for MEN1 germline mutation as well as in familial and sporadic acromegaly/pituitary adenoma patients.DesignGenomic DNA was analyzed for germline mutations in the CDKN1B/p27(Kip1) gene by PCR amplification and direct sequencing.SettingThe study was conducted at nonprofit academic research and medical centers.PatientsThirty-six Dutch and one German suspected MEN1 patient, who previously tested negative for germline MEN1 gene mutations, were analyzed. In addition, 19 familial and 50 sporadic acromegaly/pituitary adenoma patients from Europe and the United States were included in the study.Main outcome measuresWe analyzed germline CDKN1B/p27(Kip1) mutations in individuals with pituitary adenoma and MEN1-like features.ResultsA heterozygous 19-bp duplication (c.59_77dup19) leading to a truncated protein product was identified in one Dutch patient with suspected MEN1 phenotype, pituitary adenoma, carcinoid tumor, and hyperparathyroidism (one of 36, 2.8%). No mutations were detected in either familial or sporadic acromegaly/pituitary adenoma patients.ConclusionsOur results support the previous finding that germline CDKN1B/p27(Kip1) mutations predispose to a human MEN1-like condition. However, such mutations appear uncommon in suspected MEN1 cases and rare or nonexistent in familial or sporadic acromegaly/pituitary adenoma patients.

Original publication




Journal article


The Journal of clinical endocrinology and metabolism

Publication Date





3321 - 3325


Department of Medical Genetics, University of Helsinki, Finland.


Humans, Multiple Endocrine Neoplasia Type 1, Intracellular Signaling Peptides and Proteins, DNA, Immunohistochemistry, Reverse Transcriptase Polymerase Chain Reaction, DNA Mutational Analysis, Amino Acid Sequence, Germ-Line Mutation, Computer Simulation, Molecular Sequence Data, Cyclin-Dependent Kinase Inhibitor p27