Integrated genomic characterization of adrenocortical carcinoma

被引：508

作者：

Assie, Guillaume ^{[1
,2
,3
,4
]}

Letouze, Eric ^{[5
]}

Fassnacht, Martin ^{[6
,8
]}

Jouinot, Anne ^{[1
,2
,3
]}

Luscap, Windy ^{[1
,2
,3
]}

Barreau, Olivia ^{[1
,2
,3
,4
]}

Omeiri, Hanin ^{[1
,2
,3
]}

Rodriguez, Stephanie ^{[1
,2
,3
]}

Perlemoine, Karine ^{[1
,2
,3
]}

Rene-Corail, Fernande ^{[1
,2
,3
]}

Elarouci, Nabila ^{[5
]}

Sbiera, Silviu ^{[6
,7
]}

Kroiss, Matthias ^{[8
]}

Allolio, Bruno ^{[7
]}

Waldmann, Jens ^{[9
]}

Quinkler, Marcus ^{[10
]}

Mannelli, Massimo ^{[11
]}

Mantero, Franco ^{[12
]}

Papathomas, Thomas ^{[13
]}

De Krijger, Ronald ^{[13
]}

Tabarin, Antoine ^{[14
,15
]}

Kerlan, Veronique ^{[15
,16
]}

Baudin, Eric ^{[15
,17
]}

Tissier, Frederique ^{[1
,2
,3
,18
]}

Dousset, Bertrand ^{[1
,2
,3
,4
,19
]}

Groussin, Lionel ^{[1
,2
,3
,4
]}

Amar, Laurence ^{[20
]}

Clauser, Eric ^{[21
]}

Bertagna, Xavier ^{[1
,2
,3
,4
,15
]}

Ragazzon, Bruno ^{[1
,2
,3
]}

Beuschlein, Felix ^{[6
]}

Libe, Rossella ^{[1
,2
,3
,4
,15
]}

de Reynies, Aurelien ^{[5
]}

Bertherat, Jerome ^{[1
,2
,3
,4
,15
]}

机构：

[1] INSERM, Inst Cochin, U1016, Paris, France

[2] CNRS, UMR 8104, Paris, France

[3] Univ Paris 05, Sorbonne Paris Cite, Paris, France

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

[5] Ligue Natl Canc, Programme Cartes Identite Tumeurs CIT, Paris, France

[6] Univ Munich, Klinikum Univ Munchen, Med Klin & Poliklin 4, Munich, Germany

[7] Univ Hosp Wurzburg, Dept Internal Med 1, Endocrine & Diabet Unit, Wurzburg, Germany

[8] Univ Wurzburg, Comprehens Canc Ctr Mainfranken, D-97070 Wurzburg, Germany

[9] Univ Hosp Giessen & Marburg, Marburg, Germany

[10] Charite, Charite Campus Mitte, Dept Clin Epidemiol, D-13353 Berlin, Germany

[11] Univ Florence, Dept Expt & Clin Biomed Sci, Florence, Italy

[12] Univ Padua, Dept Med, Endocrinol Unit, Padua, Italy

[13] Erasmus MC Univ Med Ctr, Josephine Nefkens Inst, Dept Pathol, Rotterdam, Netherlands

[14] Univ Hosp Bordeaux, Dept Endocrinol Diabet & Metab Dis, Bordeaux, France

[15] Rare Adrenal Canc Network COMETE, Paris, France

[16] Univ Hosp Brest, Dept Endocrinol Diabet & Metab Dis, Brest, France

[17] Univ Paris 11, Inst Gustave Roussy, Dept Nucl Med & Endocrine Oncol, Villejuif, France

[18] Univ Paris 06, Hop La Pitie Salpetriere, AP HP, Dept Pathol, Paris, France

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

[20] Hop Europeen Georges Pompidou, AP HP, Hypertens Unit, Paris, France

[21] Hop Cochin, AP HP, Oncogenet Lab, F-75674 Paris, France

来源：

NATURE GENETICS | 2014年 / 46卷 / 06期

关键词：

LONG NONCODING RNAS; COPY-NUMBER CHANGES; HUMAN CANCER; MOLECULAR CLASSIFICATION; TUMOR-SUPPRESSOR; MUTATIONS; GENE; EXPRESSION; MANAGEMENT; MICRORNA;

D O I：

10.1038/ng.2953

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Adrenocortical carcinomas (ACCs) are aggressive cancers originating in the cortex of the adrenal gland(1). Despite overall poor prognosis, ACC outcome is heterogeneous(2,3). We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes(4,5) (CTNNB1, TP53, CDKN2A, RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and MED12), which we validated in an independent cohort of 77 ACCs. ZNRF3, encoding a cell surface E3 ubiquitin ligase(6), was the most frequently altered gene (21%) and is a potential new tumor suppressor gene related to the beta-catenin pathway. Our integrated genomic analyses further identified two distinct molecular subgroups with opposite outcome. The C1A group of ACCs with poor outcome displayed numerous mutations and DNA methylation alterations, whereas the C1B group of ACCs with good prognosis displayed specific deregulation of two microRNA clusters. Thus, aggressive and indolent ACCs correspond to two distinct molecular entities driven by different oncogenic alterations.

引用

页码：607 / 612

页数：6

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