Mutation and methylation analysis of TP53 in adrenal carcinogenesis

To investigate the role of coding region mutation and promoter hypermethylation of TP53 in adrenocortical cancer formation. Twenty sporadic adrenocortical cancers (ACCs) and five normal adrenal tissue samples were available for analysis. Coding region mutation of TP53 in 20 ACCs was examined by poly...

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Bibliographic Details
Published in:European journal of surgical oncology 2005-06, Vol.31 (5), p.549-554
Main Authors: Sidhu, S, Martin, E, Gicquel, C, Melki, J, Clark, S J, Campbell, P, Magarey, C J, Schulte, K M, Röher, H D, Delbridge, L, Robinson, B G
Format: Article
Language:English
Subjects:
Adrenal Gland Neoplasms - genetics
Adrenal Gland Neoplasms - metabolism
Adult
Aged
DNA Methylation
Female
Genes, p53
Humans
Male
Middle Aged
Mutation
Polymerase Chain Reaction
Prognosis
Promoter Regions, Genetic
Sequence Analysis
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Summary:To investigate the role of coding region mutation and promoter hypermethylation of TP53 in adrenocortical cancer formation. Twenty sporadic adrenocortical cancers (ACCs) and five normal adrenal tissue samples were available for analysis. Coding region mutation of TP53 in 20 ACCs was examined by polymerase chain amplification using intronic primers for exons 2-11 and direct sequencing of the product. In 10 ACCs and five normal adrenal tissue specimens, methylation of the 16 CpG sites within the TP53 promoter was examined using bisulphite methylation sequencing. Coding region mutation in TP53 was demonstrated in 5 of 20 ACCs. There were four mis-sense mutations and one frameshift mutation. Four of 5 patients with a TP53 mutation had metastases at diagnosis or detected soon thereafter and 3 of 4 died of disease within 12 months of surgical resection. No methylation was seen in the TP53 promoter in 10 ACC and the five normal adrenal tissues examined. Coding region mutation in TP53 occurs in 25% of ACCs with a trend toward a poorer prognosis. Promoter methylation of TP53 is not present in ACC as a mechanism for tumour suppressor gene (TSG) inactivation and, therefore, other genes in the 17p13 region are implicated in adrenal carcinogenesis.
ISSN:0748-7983
DOI:10.1016/j.ejso.2005.01.013