Metastatic adrenocortical carcinoma displays higher mutation rate and tumor heterogeneity than primary tumors

被引：61

作者：

Gara, Sudheer Kumar ^{[1
]}

Lack, Justin ^{[2
]}

Zhang, Lisa ^{[1
]}

Harris, Emerson ^{[1
]}

Cam, Margaret ^{[2
]}

Kebebew, Electron ^{[1
,3
,4
]}

机构：

[1] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA

[2] NCI, Ctr Canc Res, Collaborat Bioinformat Resource, NIH, Bethesda, MD 20892 USA

[3] Stanford Univ, Dept Surg, Stanford, CA 94305 USA

[4] Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

美国国家卫生研究院;

关键词：

RETINOIC ACID; GENOMIC CHARACTERIZATION; SOMATIC MUTATION; LUNG-CANCER; PHASE-II; SUNITINIB; GENE; LANDSCAPE; VARIANTS; PATTERNS;

D O I：

10.1038/s41467-018-06366-z

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：

Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and high mortality due to metastatic disease. All reported genetic alterations have been in primary ACC, and it is unknown if there is molecular heterogeneity in ACC. Here, we report the genetic changes associated with metastatic ACC compared to primary ACCs and tumor heterogeneity. We performed whole-exome sequencing of 33 metastatic tumors. The overall mutation rate (per megabase) in metastatic tumors was 2.8-fold higher than primary ACC tumor samples. We found tumor heterogeneity among different metastatic sites in ACC and discovered recurrent mutations in several novel genes. We observed 37-57% overlap in genes that are mutated among different metastatic sites within the same patient. We also identified new therapeutic targets in recurrent and metastatic ACC not previously described in primary ACCs.

引用

页数：11

共 53 条

[1] Integrated genomic characterization of adrenocortical carcinoma [J].

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 .

NATURE GENETICS, 2014, 46 (06) :607-612

[2] Whole-Exome Sequencing of Metastatic Cancer and Biomarkers of Treatment Response [J].

Beltran, Himisha ;

Eng, Kenneth ;

Mosquera, Juan Miguel ;

Sigaras, Alexandros ;

Romanel, Alessandro ;

Rennert, Hanna ;

Kossai, Myriam ;

Pauli, Chantal ;

Faltas, Bishoy ;

Fontugne, Jacqueline ;

Park, Kyung ;

Banfelder, Jason ;

Prandi, Davide ;

Madhukar, Neel ;

Zhang, Tuo ;

Padilla, Jessica ;

Greco, Noah ;

McNary, Terra J. ;

Herrscher, Erick ;

Wilkes, David ;

MacDonald, Theresa Y. ;

Xue, Hui ;

Vacic, Vladimir ;

Emde, Anne-Katrin ;

Oschwald, Dayna ;

Tan, Adrian Y. ;

Chen, Zhengming ;

Collins, Colin ;

Gleave, Martin E. ;

Wang, Yuzhuo ;

Chakravarty, Dimple ;

Schiffman, Marc ;

Kim, Robert ;

Campagne, Fabien ;

Robinson, Brian D. ;

Nanus, David M. ;

Tagawa, Scott T. ;

Xiang, Jenny Z. ;

Smogorzewska, Agata ;

Demichelis, Francesca ;

Rickman, David S. ;

Sboner, Andrea ;

Elemento, Olivier ;

Rubin, Mark A. .

JAMA ONCOLOGY, 2015, 1 (04) :466-474

[3] A case report in favor of a multistep adrenocortical tumorigenesis [J].

Bernard, MH ;

Sidhu, S ;

Berger, N ;

Peix, JL ;

Marsh, DJ ;

Robinson, BG ;

Gaston, V ;

Le Bouc, Y ;

Gicquel, C .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (03) :998-1001

[4] Invariance and sensitivity to intensity in neural discrimination of natural sounds [J].

Billimoria, Cyrus P. ;

Kraus, Benjamin J. ;

Narayan, Rajiv ;

Maddox, Ross K. ;

Sen, Kamal .

JOURNAL OF NEUROSCIENCE, 2008, 28 (25) :6304-6308

[5] Trimmomatic: a flexible trimmer for Illumina sequence data [J].

Bolger, Anthony M. ;

Lohse, Marc ;

Usadel, Bjoern .

BIOINFORMATICS, 2014, 30 (15) :2114-2120

[6] Absolute quantification of somatic DNA alterations in human cancer [J].

Carter, Scott L. ;

Cibulskis, Kristian ;

Helman, Elena ;

McKenna, Aaron ;

Shen, Hui ;

Zack, Travis ;

Laird, Peter W. ;

Onofrio, Robert C. ;

Winckler, Wendy ;

Weir, Barbara A. ;

Beroukhim, Rameen ;

Pellman, David ;

Levine, Douglas A. ;

Lander, Eric S. ;

Meyerson, Matthew ;

Getz, Gad .

NATURE BIOTECHNOLOGY, 2012, 30 (05) :413-+

[7] A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC [J].

Chau, N. G. ;

Hotte, S. J. ;

Chen, E. X. ;

Chin, S. F. ;

Turner, S. ;

Wang, L. ;

Siu, L. L. .

ANNALS OF ONCOLOGY, 2012, 23 (06) :1562-1570

[8] Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples [J].

Cibulskis, Kristian ;

Lawrence, Michael S. ;

Carter, Scott L. ;

Sivachenko, Andrey ;

Jaffe, David ;

Sougnez, Carrie ;

Gabriel, Stacey ;

Meyerson, Matthew ;

Lander, Eric S. ;

Getz, Gad .

NATURE BIOTECHNOLOGY, 2013, 31 (03) :213-219

[9] Multiple rare genetic variants co-segregating with familial IgA nephropathy all act within a single immune-related network [J].

Cox, S. N. ;

Pesce, F. ;

Moustafa, J. S. El-Sayed ;

Sallustio, F. ;

Serino, G. ;

Kkoufou, C. ;

Giampetruzzi, A. ;

Ancona, N. ;

Falchi, M. ;

Schena, F. P. .

JOURNAL OF INTERNAL MEDICINE, 2017, 281 (02) :189-205

[10] Bioinformatic prediction and functional characterization of human KIAA0100 gene [J].

Cui, He ;

Lan, Xi ;

Lu, Shemin ;

Zhang, Fujun ;

Zhang, Wanggang .

JOURNAL OF PHARMACEUTICAL ANALYSIS, 2017, 7 (01) :10-18

← 1 2 3 4 5 6 →