Objective: To evaluate the roles of the CDKN1C (P57KIP2) gene, which encodes for the cyclin-dependent kinase inhibitor CDNC, and the TP53 tumor suppressor gene in adrenal tumorigenesis, as a means of investigating the molecular basis of sporadic adrenal tumors, which is unknown.
Design: Screening for the presence CDKN1C and TP53 mutations and analyzing the expression pattern of CDNC, P53 and its downstream effector CDN1 (P21WAF1/CIP1) in a series of 79 sporadic adrenal tumors.
Methods: Single-strand conformation polymorphism and sequencing were used for mutation analysis of CDKN1C and TP53 in blood and adrenal tissue samples. In a subgroup of 48 tissues, CDKN1C expression was evaluated by RT-PCR and immunohistochemistry. Immunohistochemical analysis of P53 and CDN1 was performed.
Results: No somatic mutations of CDKN1C were found in the tumors analyzed, in spite of low/absent CDNC expression in adrenocortical adenomas and carcinomas. Mutations in the TP53 gene were present in 70% of adrenocortical carcinomas, associated with abnormal P53 and CDN1 expression, but not in benign neoplasms. In the normal adrenal cortex, CDNC expression was strictly nuclear and confined to the cortical zone (i.e. zona glomerulosa and reticularis), with no staining in the medulla.
Conclusions: Mutations in the TP53 gene are frequent in adrenocortical carcinomas and might be used as a marker of malignancy. In the normal adrenal cortex, the zone-specific pattern of expression of CDNC suggests a role in adrenal differentiation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1530/eje.0.1450207 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The molecular genetics of adrenal cushing.
Hormones (Athens)
December 2024
Genomic and Signaling of Endocrine Tumors team, INSERM U1016, CNRS UMR8104, Cochin Institute, Paris Cité University, Paris, 75005, France.
Article Synopsis
- - Adrenal Cushing accounts for 20% of cases of hypercorticism, with unilateral cortisol-producing adenomas (benign tumors) being more common than malignant adrenocortical carcinoma (ACC) and bilateral adrenal diseases.
- - Key signaling pathways involved in these tumors include protein kinase A and Wnt/β-catenin, with genetic predispositions identified through research on familial cases and pangenomic sequencing.
- - ACC is often linked to TP53 mutations, particularly in children, and can be associated with various hereditary syndromes, while cortisol-producing adenomas show mutations primarily in PRKACA and CTNNB1.
Pathogenic Germline Variants in Cancer Susceptibility Genes in Children and Young Adults With Rhabdomyosarcoma.
JCO Precis Oncol
March 2022
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Unlabelled: Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and accounts for 3% of all pediatric cancer. In this study, we investigated germline sequence and structural variation in a broad set of genes in two large, independent RMS cohorts.
Materials And Methods: Genome sequencing of the discovery cohort (n = 273) and exome sequencing of the secondary cohort (n = 121) were conducted on germline DNA.
p57KIP2‑mediated inhibition of human trophoblast apoptosis and promotion of invasion in vitro.
Int J Mol Med
July 2019
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Placental hypoxia serves a role in the early stages of normal pregnancy and is involved in the pathophysiology of preeclampsia. Previously, it was suggested that p57kinase inhibitory protein (KIP)2 regulates the cell cycle during embryogenesis and apoptosis. Recent evidence has indicated that p57KIP2 is increased in preeclamptic placentas and absence of p57KIP2 induces preeclampsia‑type symptoms in rats.
View Article and Find Full Text PDFThe ING1a model of rapid cell senescence.
Mech Ageing Dev
January 2019
Arnie Charbonneau Cancer Institute, Departments of Biochemistry and Molecular Biology and Oncology, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, T2N 4N1, Canada. Electronic address:
Replicative capacity of normal human cells decreases as telomeric sequence is lost at each division. It is believed that when a subset of chromosomes reach a critically short length, an ATM-initiated and p53-mediated transcriptional response inhibits cell growth, promoting cell senescence. In addition to loss of telomeric sequence, senescence can be induced by other stresses including ionizing radiation, oxidative damage, chemical crosslinkers like the chemotherapeutic agent cisplatin, as well as overactivation of oncogenes and tumor suppressors.
View Article and Find Full Text PDFRNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas.
BMC Cancer
April 2018
Department of Cellular Biology and Immunology, Severo Ochoa Molecular Biology Center (CBMSO), CSIC-Madrid Autonomous University, 28049, Madrid, Spain.
Background: Precursor T-cell lymphoblastic lymphomas (T-LBL) are rare aggressive hematological malignancies that mainly develop in children. As in other cancers, the loss of cell cycle control plays a prominent role in the pathogenesis in these malignancies that is primarily attributed to loss of CDKN2A (encoding protein p16INK4A). However, the impact of the deregulation of other genes such as CDKN1C, E2F1, and TP53 remains to be clarified.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!