Molecular analysis of CDKN1C and TP53 in sporadic adrenal tumors.
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.


METHODS
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.
Barzon
L
L
Department of Medical and Surgical Sciences, Division of Endocrinology, University of Padova, Padova, Italy.
Chilosi
M
M
Fallo
F
F
Martignoni
G
G
Montagna
L
L
Palù
G
G
Boscaro
M
M
D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism; D018246:Adrenocortical Adenoma / Q000235:genetics* / Q000378:metabolism; D018268:Adrenocortical Carcinoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53