一例罕见的分泌醛固酮的肾上腺皮质癌的全外显子测序

Whole-exome sequencing for a rare case of aldosterone-producing adrenocortical carcinoma

目的拟对一例分泌醛固酮的肾上腺皮质癌(ACC)进行全外显子测序分析,筛选与分泌醛固酮的ACC发生发展相关的突变基因。方法选取分泌醛固酮的ACC患者一例;收集患者的临床资料;并取患者的肿瘤组织的石蜡切片及患者的外周血,提取DNA,进行全外显子测序;分析患者的胚系突变和肿瘤组织中的体系突变。结果在患者外周血DNA中未发现已报道的与遗传性肾上腺皮质肿瘤及家族性醛固酮增多症相关的致病基因变异。在肿瘤组织中共发现349个体系基因突变,突变基因主要富集在肿瘤发生和钙信号等通路上。CTNNB1、CDKN2A和MSH6等与肾上腺肿瘤生长相关的基因发生了突变,但未发现与醛固酮合成有关的KCNJ5、ATP1A1、ATP2B3和CACNA1D等基因突变。结论该例分泌醛固酮的ACC的肿瘤发生与CTNNB1、CDKN2A和MSH6等基因突变有关,但其醛固酮合成增加的机制仍不明确。

Objective Aldosterone-producing adrenocortical carcinoma(ACC)is an uncommon disease.In this paper,the genetic mutations of aldosterone-producing ACC are studied by whole-exome sequencing.MethodsClinical data of the patient with aldosterone-producing ACC were collected.DNA was extracted from paraffin-embedded tissues and peripheral blood,then the whole-exome sequencing was carried out to identify germline and somatic mutations.Results There was no mutation associated with hereditary adrenocortical tumors and familial hyperaldosteronism in peripheral blood DNA.A total of 349 somatic mutations were found in tumor tissues,which were mainly enriched in tumorigenesis and calcium signaling pathways.Mutations related to the growth of adrenocortical tumor,CTNNB1,CDKN2A and MSH6,were detected,while no mutation related to aldosterone synthesis as KCNJ5,ATP1A1,ATP2B3 and CACNA1D was found in the tumor tissue.Conclusions The tumor-igenesis of aldosterone-producing ACC is related to CTNNB1,CDKN2A and MSH6,but the mechanism of promoting aldosterone production is still uncertain.