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
Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
Eur J Surg Oncol. 2005 Jun;31(5):549-54. doi: 10.1016/j.ejso.2005.01.013.
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.
探讨TP53编码区突变及启动子高甲基化在肾上腺皮质癌形成中的作用。
选取20例散发性肾上腺皮质癌（ACC）及5例正常肾上腺组织样本进行分析。采用针对外显子2 - 11的内含子引物通过聚合酶链反应扩增检测20例ACC中TP53的编码区突变，并对产物进行直接测序。在10例ACC及5例正常肾上腺组织标本中，采用亚硫酸氢盐甲基化测序检测TP53启动子内16个CpG位点的甲基化情况。
20例ACC中有5例存在TP53编码区突变。其中有4例错义突变和1例移码突变。5例TP53突变患者中有4例在诊断时或此后不久出现转移，4例中有3例在手术切除后12个月内死于疾病。在检测的10例ACC及5例正常肾上腺组织中，未发现TP53启动子存在甲基化。
25%的ACC存在TP53编码区突变，且预后有较差的趋势。ACC中不存在TP53启动子甲基化作为肿瘤抑制基因（TSG）失活的机制，因此，17p13区域的其他基因与肾上腺肿瘤发生有关。
