» Articles » PMID: 12955092

Cyclin D1 Gene (CCND1) Mutations in Endometrial Cancer

Overview
Journal Oncogene
Date 2003 Sep 5
PMID 12955092
Citations 56
Authors
Affiliations
Soon will be listed here.
Abstract

Cyclin D1 is frequently overexpressed in human neoplasias by gene rearrangement and amplification, but no mutations in the CCND1 gene have so far been reported. However, in vitro mutagenesis of CCND1 has shown that substitutions affecting threonine 286 residue produced cyclin D1 nuclear accumulation, by interfering with protein degradation and induced neoplastic transformation in murine fibroblasts. To test whether similar genetic changes may occur in vivo, we analysed a series of 60 endometrioid endometrial carcinomas (EECs) for cyclin D1 expression and gene amplification by immunohistochemistry and FISH, respectively. Two of 17 carcinomas showing cyclin D1 expression in more than 5% of neoplastic cells, but without gene amplification, were found to harbor single-base substitutions in CCND1 that changed proline 287 into threonine and serine, respectively. Both cases expressed cyclin D1 in more than 50% of neoplastic cells. Additionally, seven tumors with cyclin D1 overexpression of an independent series of 59 EECs were also analysed, and a 12-bp in-frame deletion that eliminated amino acids 289-292 was detected in one case with cylin D1 expression in more than 50% of neoplastic cells. In contrast, no mutations of the CCND1 gene were detected in a set of breast carcinomas with cyclin D1 overexpression without gene amplification. In summary, our data indicate that mutations of CCND1, which probably render the protein insensitive to degradation, represent a previously unreported mechanism of cyclin D1 overexpression in human tumors in vivo.

Citing Articles

Assessment of Cyclin D1 Expression: Prognostic Value and Functional Insights in Endometrial Cancer: In Silico Study.

Szymanski M, Jerka D, Bonowicz K, Antosik P, Gagat M Int J Mol Sci. 2025; 26(3).

PMID: 39940659 PMC: 11816803. DOI: 10.3390/ijms26030890.


Quantity and quality of minichromosome maintenance protein complexes couple replication licensing to genome integrity.

Yadav A, Polasek-Sedlackova H Commun Biol. 2024; 7(1):167.

PMID: 38336851 PMC: 10858283. DOI: 10.1038/s42003-024-05855-w.


A biomarker and molecular mechanism investigation for thyroid cancer.

Xie K Cent Eur J Immunol. 2023; 48(3):203-218.

PMID: 37901864 PMC: 10604643. DOI: 10.5114/ceji.2023.132163.


Integrating bulk and single-cell data to predict the prognosis and identify the immune landscape in HNSCC.

Yang C, Cheng X, Gao S, Pan Q J Cell Mol Med. 2023; 28(1):e18009.

PMID: 37882107 PMC: 10805493. DOI: 10.1111/jcmm.18009.


Histopathological and Immunohistochemical Prognostic Factors in High-Grade Non-Endometrioid Carcinomas of the Endometrium (HG-NECs): Is It Possible to Identify Subgroups at Increased Risk?.

Paudice M, Biatta C, Scaglione G, Parodi A, Mammoliti S, Moioli M Diagnostics (Basel). 2023; 13(13).

PMID: 37443564 PMC: 10341374. DOI: 10.3390/diagnostics13132171.