Inactivation of the APC Gene Is Constant in Adrenocortical Tumors from Patients with Familial Adenomatous Polyposis but Not Frequent in Sporadic Adrenocortical Cancers

被引：94

作者：

Gaujoux, Sebastien ^{[1
,2
,3
]}

Pinson, Stephane ^{[12
]}

Gimenez-Roqueplo, Anne-Paule ^{[6
,9
,10
]}

Amar, Laurence ^{[7
]}

Ragazzon, Bruno ^{[1
,2
]}

Launay, Pierre ^{[1
,2
]}

Meatchi, Tchao ^{[8
]}

Libe, Rossella ^{[1
,2
,4
,10
]}

Bertagna, Xavier ^{[1
,2
,4
,10
]}

Audebourg, Anne ^{[5
]}

Zucman-Rossi, Jessica ^{[11
]}

Tissier, Frederique ^{[1
,2
,5
,10
]}

Bertherat, Jerome ^{[1
,2
,4
,10
]}

机构：

[1] Univ Paris 05, Inst Cochin, Fac Med, CNRS,UMR 8104, Paris, France

[2] INSERM, U1016, Paris, France

[3] Hop Cochin, AP HP, Dept Digest & Endocrine Surg, F-75674 Paris, France

[4] Hop Cochin, AP HP, Dept Endocrinol, Ctr Rare Adrenal Dis, F-75674 Paris, France

[5] Hop Cochin, AP HP, Dept Pathol, F-75674 Paris, France

[6] Hop Europeen Georges Pompidou, AP HP, Dept Genet, Paris, France

[7] Hop Europeen Georges Pompidou, AP HP, Dept Hypertens, Paris, France

[8] Hop Europeen Georges Pompidou, AP HP, Dept Pathol, Paris, France

[9] Paris Cardiovasc Res Ctr HEGP, INSERM, UMR 970, Paris, France

[10] INCa, Rare Adrenal Canc Reference Ctr COMETE, Paris, France

[11] INSERM, UMR 674, Paris, France

[12] Hop Edouard Herriot, HCL, Serv Genet Clin & Mol, Lyon, France

来源：

CLINICAL CANCER RESEARCH | 2010年 / 16卷 / 21期

关键词：

BETA-CATENIN GENE; FACTOR-II GENE; WILMS-TUMOR; GARDNERS-SYNDROME; WNT/BETA-CATENIN; PRKAR1A MUTATION; E1317Q VARIANT; ADRENAL MASSES; DISEASE PPNAD; CARCINOMA;

D O I：

10.1158/1078-0432.CCR-10-1497

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Purpose: In adrenocortical tumors (ACT), Wnt/beta-catenin pathway activation can be explained by beta-catenin somatic mutations only in a subset of tumors. ACT is observed in patients with familial adenomatous polyposis (FAP) with germline APC mutations, as well as in patients with Beckwith-Wiede-mann syndrome with Wilms' tumors reported to have WTX somatic mutations. Both APC and WTX are involved in Wnt/beta-catenin pathway regulation and may play a role in ACT tumorigenesis. The aim of this study was to report if APC and WTX may be associated with FAP-associated and sporadic ACT. Experimental Design: ACTs from patients with FAP and sporadic adrenocortical carcinomas (ACC) with abnormal beta-catenin localization on immunohistochemistry but no somatic beta-catenin mutations were studied. APC was analyzed by denaturing high-performance liquid chromatography followed by direct sequencing and by multiplex ligation-dependent probe amplification when allelic loss was suspected. WTX was studied by direct sequencing. Results: Four ACTs were observed in three patients with FAP and were ACC, adrenocortical adenoma, and bilateral macronodular adrenocortical hyperplasia, all with abnormal beta-catenin localization. Biallelic inactivation of APC was strongly suggested by the simultaneous existence of somatic and germline alterations in all ACTs. In the 20 sporadic ACCs, a silent heterozygous somatic mutation as well as a rare heterozygous polymorphism in APC was found. No WTX mutations were observed. Conclusions: ACT should be considered a FAP tumor. Biallelic APC inactivation mediates activation of the Wnt/beta-catenin pathway in the ACTs of patients with FAP. In contrast, APC and WTX genetic alterations do not play a significant role in sporadic ACC. Clin Cancer Res; 16(21); 5133-41. (C)2010 AACR.

引用

页码：5133 / 5141

页数：9

共 51 条

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[2]

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