Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas

被引：149

作者：

Castro-Vega, Luis Jaime ^{[1
,2
]}

Letouze, Eric ^{[3
]}

Burnichon, Nelly ^{[1
,2
,4
]}

Buffet, Alexandre ^{[1
,2
,4
]}

Disderot, Pierre-Helie ^{[1
,2
]}

Khalifa, Emmanuel ^{[1
,2
,4
]}

Loriot, Celine ^{[1
,2
]}

Elarouci, Nabila ^{[3
]}

Morin, Aurelie ^{[1
,2
]}

Menara, Melanie ^{[1
,2
]}

Lepoutre-Lussey, Charlotte ^{[1
,2
,5
]}

Badoual, Cecile ^{[1
,2
,6
]}

Sibony, Mathilde ^{[2
,7
]}

Dousset, Bertrand ^{[2
,8
,9
,10
]}

Libe, Rossella ^{[2
,9
,10
,11
,12
]}

Zinzindohoue, Franck ^{[2
,13
]}

Plouin, Pierre Francois ^{[1
,2
,5
,12
]}

Bertherat, Jerome ^{[2
,9
,10
,11
,12
]}

Amar, Laurence ^{[1
,2
,5
]}

de Reynies, Aurelien ^{[3
]}

Favier, Judith ^{[1
,2
]}

Gimenez-Roqueplo, Anne-Paule ^{[1
,2
,4
,12
]}

机构：

[1] INSERM, UMR970, Paris Cardiovasc Res Ctr, F-75015 Paris, France

[2] Univ Paris 05, Sorbonne Paris Cite, Fac Med, F-75006 Paris, France

[3] Ligue Natl Canc, Programme Cartes Identite Tumeurs, F-75013 Paris, France

[4] Hop Europe Georges Pompidou, AP HP, Dept Genet, F-75015 Paris, France

[5] Hop Europe Georges Pompidou, AP HP, Hypertens Unit, F-75015 Paris, France

[6] Hop Europe Georges Pompidou, AP HP, Dept Pathol, F-75015 Paris, France

[7] Hop Cochin, AP HP, Dept Pathol, F-75006 Paris, France

[8] Hop Cochin, AP HP, Dept Digest & Endocrine Surg, F-75006 Paris, France

[9] INSERM, U1016, Inst Cochin, F-75006 Paris, France

[10] CNRS, UMR8104, F-75006 Paris, France

[11] Hop Cochin, AP HP, Dept Endocrinol, F-75006 Paris, France

[12] Rare Adrenal Canc Network COMETE, F-75006 Paris, France

[13] Hop Europe Georges Pompidou, AP HP, Dept Surg, F-75015 Paris, France

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

MALIGNANT PHEOCHROMOCYTOMAS; SOMATIC MUTATIONS; EXPRESSION PROFILES; GENETIC LANDSCAPE; DRIVER MUTATIONS; SDHB GENE; H-RAS; CANCER; BENIGN; MICRORNAS;

D O I：

10.1038/ncomms7044

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Pheochromocytomas and paragangliomas (PCCs/PGLs) are neural crest-derived tumours with a very strong genetic component. Here we report the first integrated genomic examination of a large collection of PCC/PGL. SNP array analysis reveals distinct copy-number patterns associated with genetic background. Whole-exome sequencing shows a low mutation rate of 0.3 mutations per megabase, with few recurrent somatic mutations in genes not previously associated with PCC/PGL. DNA methylation arrays and miRNA sequencing identify DNA methylation changes and miRNA expression clusters strongly associated with messenger RNA expression profiling. Overexpression of the miRNA cluster 182/96/183 is specific in SDHB-mutated tumours and induces malignant traits, whereas silencing of the imprinted DLK1-MEG3 miRNA cluster appears as a potential driver in a subgroup of sporadic tumours. Altogether, the complete genomic landscape of PCC/PGL is mainly driven by distinct germline and/or somatic mutations in susceptibility genes and reveals different molecular entities, characterized by a set of unique genomic alterations.

引用

页数：9

共 62 条

[1] Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas
Amar, Laurence
Baudin, Eric
Burnichon, Nelly
Peyrard, Severine
Silvera, Stephane
Bertherat, Jerome
Bertagna, Xavier
Schlumberger, Martin
Jeunemaitre, Xavier
Gimenez-Roqueplo, Anne-Paule
Plouin, Pierre-Francois
[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2007, 92 (10) : 3822 - 3828
[2] Differential expression analysis for sequence count data
Anders, Simon
Huber, Wolfgang
[J]. GENOME BIOLOGY, 2010, 11 (10):
[3] Integrated genomic characterization of adrenocortical carcinoma
Assie, Guillaume
Letouze, Eric
Fassnacht, Martin
Jouinot, Anne
Luscap, Windy
Barreau, Olivia
Omeiri, Hanin
Rodriguez, Stephanie
Perlemoine, Karine
Rene-Corail, Fernande
Elarouci, Nabila
Sbiera, Silviu
Kroiss, Matthias
Allolio, Bruno
Waldmann, Jens
Quinkler, Marcus
Mannelli, Massimo
Mantero, Franco
Papathomas, Thomas
De Krijger, Ronald
Tabarin, Antoine
Kerlan, Veronique
Baudin, Eric
Tissier, Frederique
Dousset, Bertrand
Groussin, Lionel
Amar, Laurence
Clauser, Eric
Bertagna, Xavier
Ragazzon, Bruno
Beuschlein, Felix
Libe, Rossella
de Reynies, Aurelien
Bertherat, Jerome
[J]. NATURE GENETICS, 2014, 46 (06) : 607 - 612
[4] CGH and C 44/MIB-1 immunohistochemistry are helpful to distinguish metastasized from nonmetastasized sporadic pheochromocytomas
August, C
August, K
Schroeder, S
Bahn, H
Hinze, R
Baba, HA
Kersting, C
Buerger, H
[J]. MODERN PATHOLOGY, 2004, 17 (09) : 1119 - 1128
[5] MicroRNA-182 promotes leptomeningeal spread of non-sonic hedgehog-medulloblastoma
Bai, Alfa H. C.
Milde, Till
Remke, Marc
Rolli, Claudio G.
Hielscher, Thomas
Cho, Yoon-Jae
Kool, Marcel
Northcott, Paul A.
Jugold, Manfred
Bazhin, Alexandr V.
Eichmueller, Stefan B.
Kulozik, Andreas E.
Pscherer, Armin
Benner, Axel
Taylor, Michael D.
Pomeroy, Scott L.
Kemkemer, Ralf
Witt, Olaf
Korshunov, Andrey
Lichter, Peter
Pfister, Stefan M.
[J]. ACTA NEUROPATHOLOGICA, 2012, 123 (04) : 529 - 538
[6] The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis
Benetatos, Leonidas
Hatzimichael, Eleftheria
Londin, Eric
Vartholomatos, George
Loher, Phillipe
Rigoutsos, Isidore
Briasoulis, Evangelos
[J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2013, 70 (05) : 795 - 814
[7] Genome-wide DNA methylation profiling using Infinium® assay
Bibikova, Marina
Le, Jennie
Barnes, Bret
Saedinia-Melnyk, Shadi
Zhou, Lixin
Shen, Richard
Gunderson, Kevin L.
[J]. EPIGENOMICS, 2009, 1 (01) : 177 - 200
[8] Targeting the Hepatocyte Growth Factor-cMET Axis in Cancer Therapy
Blumenschein, George R., Jr.
Mills, Gordon B.
Gonzalez-Angulo, Ana M.
[J]. JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (26) : 3287 - 3296
[9] The Somatic Genomic Landscape of Glioblastoma
Brennan, Cameron W.
Verhaak, Roel G. W.
McKenna, Aaron
Campos, Benito
Noushmehr, Houtan
Salama, Sofie R.
Zheng, Siyuan
Chakravarty, Debyani
Sanborn, J. Zachary
Berman, Samuel H.
Beroukhim, Rameen
Bernard, Brady
Wu, Chang-Jiun
Genovese, Giannicola
Shmulevich, Ilya
Barnholtz-Sloan, Jill
Zou, Lihua
Vegesna, Rahulsimham
Shukla, Sachet A.
Ciriello, Giovanni
Yung, W. K.
Zhang, Wei
Sougnez, Carrie
Mikkelsen, Tom
Aldape, Kenneth
Bigner, Darell D.
Van Meir, Erwin G.
Prados, Michael
Sloan, Andrew
Black, Keith L.
Eschbacher, Jennifer
Finocchiaro, Gaetano
Friedman, William
Andrews, David W.
Guha, Abhijit
Iacocca, Mary
O'Neill, Brian P.
Foltz, Greg
Myers, Jerome
Weisenberger, Daniel J.
Penny, Robert
Kucherlapati, Raju
Perou, Charles M.
Hayes, D. Neil
Gibbs, Richard
Marra, Marco
Mills, Gordon B.
Lander, Eric
Spellman, Paul
Wilson, Richard
[J]. CELL, 2013, 155 (02) : 462 - 477
[10] Somatic NF1 inactivation is a frequent event in sporadic pheochromocytoma
Burnichon, Nelly
Buffet, Alexandre
Parfait, Beatrice
Letouze, Eric
Laurendeau, Ingrid
Loriot, Celine
Pasmant, Eric
Abermil, Nassera
Valeyrie-Allanore, Laurence
Bertherat, Jerome
Amar, Laurence
Vidaud, Dominique
Favier, Judith
Gimenez-Roqueplo, Anne-Paule
[J]. HUMAN MOLECULAR GENETICS, 2012, 21 (26) : 5397 - 5405

← 1 2 3 4 5 6 7 →