Related Experiment Video
Updated: Jul 14, 2026
09:33
Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
Published on: August 25, 2023
Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia
Marianthi Georgitsi1, Anniina Raitila, Auli Karhu
1Department of Medical Genetics, University of Helsinki, Finland.
The Journal of Clinical Endocrinology and Metabolism
|May 24, 2007
Summary
Germline CDKN1B/p27(Kip1) mutations can cause Multiple Endocrine Neoplasia type 1 (MEN1)-like conditions, but are uncommon in suspected MEN1 cases. These mutations were not found in familial or sporadic pituitary adenoma patients.
Area of Science:
- Endocrinology
- Genetics
- Oncology
Background:
- Germline mutations in the MEN1 gene cause Multiple Endocrine Neoplasia type 1 (MEN1) syndrome.
- However, up to 25% of MEN1 cases lack MEN1 gene mutations.
- Recent findings suggest CDKN1B/p27(Kip1) gene mutations may play a role in MEN1 predisposition.
Purpose of the Study:
- To investigate the role of CDKN1B/p27(Kip1) in tumor predisposition.
- To analyze patients with suspected MEN1 but negative for MEN1 mutations.
- To evaluate familial and sporadic acromegaly/pituitary adenoma patients.
Main Methods:
- Germline DNA analysis for CDKN1B/p27(Kip1) mutations using PCR and sequencing.
- Study included 37 suspected MEN1 patients negative for MEN1 mutations.
- Also included 69 familial and sporadic acromegaly/pituitary adenoma patients.
Main Results:
- A heterozygous 19-bp duplication in CDKN1B/p27(Kip1) was found in one suspected MEN1 patient (2.8%).
- This patient presented with pituitary adenoma, carcinoid tumor, and hyperparathyroidism.
- No CDKN1B/p27(Kip1) mutations were detected in familial or sporadic acromegaly/pituitary adenoma cohorts.
Conclusions:
- Germline CDKN1B/p27(Kip1) mutations can predispose to MEN1-like conditions.
- These mutations are uncommon in suspected MEN1 cases.
- Mutations are rare or absent in familial/sporadic acromegaly and pituitary adenoma.
Related Concept Videos
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:33Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...