Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

Lauren Fishbein; Ignaty Leshchiner; Vonn Walter; Ludmila Danilova; A. Gordon Robertson; Amy R. Johnson; Tara M. Lichtenberg; Bradley A. Murray; Hans K. Ghayee; Tobias Else; Shiyun Ling; Stuart R. Jefferys; Aguirre A. de Cubas; Brandon Wenz; Esther Korpershoek; Antonio L. Amelio; Liza Makowski; W. Kimryn Rathmell; Anne Paule Gimenez-Roqueplo; Thomas J. Giordano; Sylvia L. Asa; Arthur S. Tischler; Rehan Akbani; Adrian Ally; Laurence Amar; Antonio L. Amelio; Harindra Arachchi; Sylvia L. Asa; Richard J. Auchus; J. Todd Auman; Robert Baertsch; Miruna Balasundaram; Saianand Balu; Detlef K. Bartsch; Eric Baudin; Thomas Bauer; Allison Beaver; Christopher Benz; Rameen Beroukhim; Felix Beuschlein; Tom Bodenheimer; Lori Boice; Jay Bowen; Reanne Bowlby; Denise Brooks; Rebecca Carlsen; Suzie Carter; Clarissa A. Cassol; Andrew D. Cherniack; Lynda Chin; Juok Cho; Eric Chuah; Sudha Chudamani; Leslie Cope; Daniel Crain; Erin Curley; Ludmila Danilova; Aguirre A. de Cubas; Ronald R. de Krijger; John A. Demchok; Timo Deutschbein; Noreen Dhalla; David Dimmock; Winand N M Dinjens; Tobias Else; Charis Eng; Jennifer Eschbacher; Martin Fassnacht; Ina Felau; Michael Feldman; Martin L. Ferguson; Ian Fiddes; Lauren Fishbein; Scott Frazer; Stacey B. Gabriel; Johanna Gardner; Julie M. Gastier-Foster; Nils Gehlenborg; Mark Gerken; Gad Getz; Jennifer Geurts; Hans K. Ghayee; Anne Paule Gimenez-Roqueplo; Thomas J. Giordano; Mary Goldman; Kiley Graim; Manaswi Gupta; David Haan; Stefanie Hahner; Constanze Hantel; David Haussler; D. Neil Hayes; David I. Heiman; Katherine A. Hoadley; Robert A. Holt; Alan P. Hoyle; Mei Huang; Bryan Hunt; Carolyn M. Hutter; Stuart R. Jefferys; Amy R. Johnson; Steven J M Jones; Corbin D. Jones; Katayoon Kasaian; Electron Kebebew; Jaegil Kim; Patrick Kimes; Theo Knijnenburg; Esther Korpershoek; Eric Lander; Michael S. Lawrence; Ronald Lechan; Darlene Lee; Kristen M. Leraas; Antonio Lerario; Ignaty Leshchiner; Tara M. Lichtenberg; Pei Lin; Shiyun Ling; Jia Liu; Virginia A. LiVolsi; Laxmi Lolla; Yair Lotan; Yiling Lu; Yussanne Ma; Nicole Maison; Liza Makowski; David Mallery; Massimo Mannelli; Jessica Marquard; Marco A. Marra; Thomas Matthew; Michael Mayo; Tchao Méatchi; Shaowu Meng; Maria J. Merino; Ozgur Mete; Matthew Meyerson; Piotr A. Mieczkowski; Gordon B. Mills; Richard A. Moore; Olena Morozova; Scott Morris; Lisle E. Mose; Andrew J. Mungall; Bradley A. Murray; Rashi Naresh; Katherine L. Nathanson; Yulia Newton; Sam Ng; Ying Ni; Michael S. Noble; Fiemu Nwariaku; Karel Pacak; Joel S. Parker; Evan Paul; Robert Penny; Charles M. Perou; Amy H. Perou; Todd Pihl; James Powers; Jennifer Rabaglia; Amie Radenbaugh; Nilsa C. Ramirez; Arjun Rao; W. Kimryn Rathmell; Anna Riester; Jeffrey Roach; A. Gordon Robertson; Sara Sadeghi; Gordon Saksena; Sofie Salama; Charles Saller; George Sandusky; Silviu Sbiera; Jacqueline E. Schein; Steven E. Schumacher; Candace Shelton; Troy Shelton; Margi Sheth; Yan Shi; Juliann Shih; Ilya Shmulevich; Janae V. Simons; Payal Sipahimalani; Tara Skelly; Heidi J. Sofia; Artem Sokolov; Matthew G. Soloway; Carrie Sougnez; Josh Stuart; Charlie Sun; Teresa Swatloski; Angela Tam; Donghui Tan; Roy Tarnuzzer; Katherine Tarvin; Nina Thiessen; Leigh B. Thorne; Henri J. Timmers; Arthur S. Tischler; Kane Tse; Vlado Uzunangelov; Anouk van Berkel; Umadevi Veluvolu; Ales Vicha; Doug Voet; Jens Waldmann; Vonn Walter; Yunhu Wan; Zhining Wang; Tracy S. Wang; Joellen Weaver; John N. Weinstein; Dirk Weismann; Brandon Wenz; Matthew D. Wilkerson; Lisa Wise; Tina Wong; Christopher Wong; Ye Wu; Liming Yang; Tomas Zelinka; Jean C. Zenklusen; Jiashan (Julia) Zhang; Wei Zhang; Jingchun Zhu; Franck Zinzindohoué; Erik Zmuda; Karel Pacak; Katherine L. Nathanson; Matthew D. Wilkerson

doi:10.1016/j.ccell.2017.01.001

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

Lauren Fishbein, Ignaty Leshchiner, Vonn Walter, Ludmila Danilova, A. Gordon Robertson, Amy R. Johnson, Tara M. Lichtenberg, Bradley A. Murray, Hans K. Ghayee, Tobias Else, Shiyun Ling, Stuart R. Jefferys, Aguirre A. de Cubas, Brandon Wenz, Esther Korpershoek, Antonio L. Amelio, Liza Makowski, W. Kimryn Rathmell, Anne Paule Gimenez-Roqueplo, Thomas J. GiordanoSylvia L. Asa, Arthur S. Tischler, Rehan Akbani, Adrian Ally, Laurence Amar, Antonio L. Amelio, Harindra Arachchi, Sylvia L. Asa, Richard J. Auchus, J. Todd Auman, Robert Baertsch, Miruna Balasundaram, Saianand Balu, Detlef K. Bartsch, Eric Baudin, Thomas Bauer, Allison Beaver, Christopher Benz, Rameen Beroukhim, Felix Beuschlein, Tom Bodenheimer, Lori Boice, Jay Bowen, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Suzie Carter, Clarissa A. Cassol, Andrew D. Cherniack, Lynda Chin, Juok Cho, Eric Chuah, Sudha Chudamani, Leslie Cope, Daniel Crain, Erin Curley, Ludmila Danilova, Aguirre A. de Cubas, Ronald R. de Krijger, John A. Demchok, Timo Deutschbein, Noreen Dhalla, David Dimmock, Winand N M Dinjens, Tobias Else, Charis Eng, Jennifer Eschbacher, Martin Fassnacht, Ina Felau, Michael Feldman, Martin L. Ferguson, Ian Fiddes, Lauren Fishbein, Scott Frazer, Stacey B. Gabriel, Johanna Gardner, Julie M. Gastier-Foster, Nils Gehlenborg, Mark Gerken, Gad Getz, Jennifer Geurts, Hans K. Ghayee, Anne Paule Gimenez-Roqueplo, Thomas J. Giordano, Mary Goldman, Kiley Graim, Manaswi Gupta, David Haan, Stefanie Hahner, Constanze Hantel, David Haussler, D. Neil Hayes, David I. Heiman, Katherine A. Hoadley, Robert A. Holt, Alan P. Hoyle, Mei Huang, Bryan Hunt, Carolyn M. Hutter, Stuart R. Jefferys, Amy R. Johnson, Steven J M Jones, Corbin D. Jones, Katayoon Kasaian, Electron Kebebew, Jaegil Kim, Patrick Kimes, Theo Knijnenburg, Esther Korpershoek, Eric Lander, Michael S. Lawrence, Ronald Lechan, Darlene Lee, Kristen M. Leraas, Antonio Lerario, Ignaty Leshchiner, Tara M. Lichtenberg, Pei Lin, Shiyun Ling, Jia Liu, Virginia A. LiVolsi, Laxmi Lolla, Yair Lotan, Yiling Lu, Yussanne Ma, Nicole Maison, Liza Makowski, David Mallery, Massimo Mannelli, Jessica Marquard, Marco A. Marra, Thomas Matthew, Michael Mayo, Tchao Méatchi, Shaowu Meng, Maria J. Merino, Ozgur Mete, Matthew Meyerson, Piotr A. Mieczkowski, Gordon B. Mills, Richard A. Moore, Olena Morozova, Scott Morris, Lisle E. Mose, Andrew J. Mungall, Bradley A. Murray, Rashi Naresh, Katherine L. Nathanson, Yulia Newton, Sam Ng, Ying Ni, Michael S. Noble, Fiemu Nwariaku, Karel Pacak, Joel S. Parker, Evan Paul, Robert Penny, Charles M. Perou, Amy H. Perou, Todd Pihl, James Powers, Jennifer Rabaglia, Amie Radenbaugh, Nilsa C. Ramirez, Arjun Rao, W. Kimryn Rathmell, Anna Riester, Jeffrey Roach, A. Gordon Robertson, Sara Sadeghi, Gordon Saksena, Sofie Salama, Charles Saller, George Sandusky, Silviu Sbiera, Jacqueline E. Schein, Steven E. Schumacher, Candace Shelton, Troy Shelton, Margi Sheth, Yan Shi, Juliann Shih, Ilya Shmulevich, Janae V. Simons, Payal Sipahimalani, Tara Skelly, Heidi J. Sofia, Artem Sokolov, Matthew G. Soloway, Carrie Sougnez, Josh Stuart, Charlie Sun, Teresa Swatloski, Angela Tam, Donghui Tan, Roy Tarnuzzer, Katherine Tarvin, Nina Thiessen, Leigh B. Thorne, Henri J. Timmers, Arthur S. Tischler, Kane Tse, Vlado Uzunangelov, Anouk van Berkel, Umadevi Veluvolu, Ales Vicha, Doug Voet, Jens Waldmann, Vonn Walter, Yunhu Wan, Zhining Wang, Tracy S. Wang, Joellen Weaver, John N. Weinstein, Dirk Weismann, Brandon Wenz, Matthew D. Wilkerson, Lisa Wise, Tina Wong, Christopher Wong, Ye Wu, Liming Yang, Tomas Zelinka, Jean C. Zenklusen, Jiashan (Julia) Zhang, Wei Zhang, Jingchun Zhu, Franck Zinzindohoué, Erik Zmuda, Karel Pacak, Katherine L. Nathanson, Matthew D. Wilkerson

Research output: Contribution to journal › Article › Academic › peer-review

1 Citation (Scopus)

Abstract

We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.

Original language	English
Pages (from-to)	181-193
Number of pages	13
Journal	Cancer Cell
Volume	31
Issue number	2
DOIs	https://doi.org/10.1016/j.ccell.2017.01.001
Publication status	Published - 13 Feb 2017

Keywords

CSDE1
expression subtypes
genomics
MAML3
metastasis
molecular profiling
paraganglioma
pheochromocytoma
sequencing
TCGA

Access to Document

10.1016/j.ccell.2017.01.001

Cite this

Fishbein, L., Leshchiner, I., Walter, V., Danilova, L., Robertson, A. G., Johnson, A. R., Lichtenberg, T. M., Murray, B. A., Ghayee, H. K., Else, T., Ling, S., Jefferys, S. R., de Cubas, A. A., Wenz, B., Korpershoek, E., Amelio, A. L., Makowski, L., Rathmell, W. K., Gimenez-Roqueplo, A. P., ... Wilkerson, M. D. (2017). Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma. Cancer Cell, 31(2), 181-193. https://doi.org/10.1016/j.ccell.2017.01.001

@article{310fae89681b41da8fcc62f7eae57a17,

title = "Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma",

abstract = "We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.",

keywords = "CSDE1, expression subtypes, genomics, MAML3, metastasis, molecular profiling, paraganglioma, pheochromocytoma, sequencing, TCGA",

author = "Lauren Fishbein and Ignaty Leshchiner and Vonn Walter and Ludmila Danilova and Robertson, {A. Gordon} and Johnson, {Amy R.} and Lichtenberg, {Tara M.} and Murray, {Bradley A.} and Ghayee, {Hans K.} and Tobias Else and Shiyun Ling and Jefferys, {Stuart R.} and {de Cubas}, {Aguirre A.} and Brandon Wenz and Esther Korpershoek and Amelio, {Antonio L.} and Liza Makowski and Rathmell, {W. Kimryn} and Gimenez-Roqueplo, {Anne Paule} and Giordano, {Thomas J.} and Asa, {Sylvia L.} and Tischler, {Arthur S.} and Rehan Akbani and Adrian Ally and Laurence Amar and Amelio, {Antonio L.} and Harindra Arachchi and Asa, {Sylvia L.} and Auchus, {Richard J.} and Auman, {J. Todd} and Robert Baertsch and Miruna Balasundaram and Saianand Balu and Bartsch, {Detlef K.} and Eric Baudin and Thomas Bauer and Allison Beaver and Christopher Benz and Rameen Beroukhim and Felix Beuschlein and Tom Bodenheimer and Lori Boice and Jay Bowen and Reanne Bowlby and Denise Brooks and Rebecca Carlsen and Suzie Carter and Cassol, {Clarissa A.} and Cherniack, {Andrew D.} and Lynda Chin and Juok Cho and Eric Chuah and Sudha Chudamani and Leslie Cope and Daniel Crain and Erin Curley and Ludmila Danilova and {de Cubas}, {Aguirre A.} and {de Krijger}, {Ronald R.} and Demchok, {John A.} and Timo Deutschbein and Noreen Dhalla and David Dimmock and Dinjens, {Winand N M} and Tobias Else and Charis Eng and Jennifer Eschbacher and Martin Fassnacht and Ina Felau and Michael Feldman and Ferguson, {Martin L.} and Ian Fiddes and Lauren Fishbein and Scott Frazer and Gabriel, {Stacey B.} and Johanna Gardner and Gastier-Foster, {Julie M.} and Nils Gehlenborg and Mark Gerken and Gad Getz and Jennifer Geurts and Ghayee, {Hans K.} and Gimenez-Roqueplo, {Anne Paule} and Giordano, {Thomas J.} and Mary Goldman and Kiley Graim and Manaswi Gupta and David Haan and Stefanie Hahner and Constanze Hantel and David Haussler and Hayes, {D. Neil} and Heiman, {David I.} and Hoadley, {Katherine A.} and Holt, {Robert A.} and Hoyle, {Alan P.} and Mei Huang and Bryan Hunt and Hutter, {Carolyn M.} and Jefferys, {Stuart R.} and Johnson, {Amy R.} and Jones, {Steven J M} and Jones, {Corbin D.} and Katayoon Kasaian and Electron Kebebew and Jaegil Kim and Patrick Kimes and Theo Knijnenburg and Esther Korpershoek and Eric Lander and Lawrence, {Michael S.} and Ronald Lechan and Darlene Lee and Leraas, {Kristen M.} and Antonio Lerario and Ignaty Leshchiner and Lichtenberg, {Tara M.} and Pei Lin and Shiyun Ling and Jia Liu and LiVolsi, {Virginia A.} and Laxmi Lolla and Yair Lotan and Yiling Lu and Yussanne Ma and Nicole Maison and Liza Makowski and David Mallery and Massimo Mannelli and Jessica Marquard and Marra, {Marco A.} and Thomas Matthew and Michael Mayo and Tchao M{\'e}atchi and Shaowu Meng and Merino, {Maria J.} and Ozgur Mete and Matthew Meyerson and Mieczkowski, {Piotr A.} and Mills, {Gordon B.} and Moore, {Richard A.} and Olena Morozova and Scott Morris and Mose, {Lisle E.} and Mungall, {Andrew J.} and Murray, {Bradley A.} and Rashi Naresh and Nathanson, {Katherine L.} and Yulia Newton and Sam Ng and Ying Ni and Noble, {Michael S.} and Fiemu Nwariaku and Karel Pacak and Parker, {Joel S.} and Evan Paul and Robert Penny and Perou, {Charles M.} and Perou, {Amy H.} and Todd Pihl and James Powers and Jennifer Rabaglia and Amie Radenbaugh and Ramirez, {Nilsa C.} and Arjun Rao and Rathmell, {W. Kimryn} and Anna Riester and Jeffrey Roach and Robertson, {A. Gordon} and Sara Sadeghi and Gordon Saksena and Sofie Salama and Charles Saller and George Sandusky and Silviu Sbiera and Schein, {Jacqueline E.} and Schumacher, {Steven E.} and Candace Shelton and Troy Shelton and Margi Sheth and Yan Shi and Juliann Shih and Ilya Shmulevich and Simons, {Janae V.} and Payal Sipahimalani and Tara Skelly and Sofia, {Heidi J.} and Artem Sokolov and Soloway, {Matthew G.} and Carrie Sougnez and Josh Stuart and Charlie Sun and Teresa Swatloski and Angela Tam and Donghui Tan and Roy Tarnuzzer and Katherine Tarvin and Nina Thiessen and Thorne, {Leigh B.} and Timmers, {Henri J.} and Tischler, {Arthur S.} and Kane Tse and Vlado Uzunangelov and {van Berkel}, Anouk and Umadevi Veluvolu and Ales Vicha and Doug Voet and Jens Waldmann and Vonn Walter and Yunhu Wan and Zhining Wang and Wang, {Tracy S.} and Joellen Weaver and Weinstein, {John N.} and Dirk Weismann and Brandon Wenz and Wilkerson, {Matthew D.} and Lisa Wise and Tina Wong and Christopher Wong and Ye Wu and Liming Yang and Tomas Zelinka and Zenklusen, {Jean C.} and Zhang, {Jiashan (Julia)} and Wei Zhang and Jingchun Zhu and Franck Zinzindohou{\'e} and Erik Zmuda and Karel Pacak and Nathanson, {Katherine L.} and Wilkerson, {Matthew D.}",

note = "Funding Information: We thank all of the patients and families who contributed to the study, Ina Felau for project management, and Jill Dolinsky, MS, CGC, at Ambry Genetics, Inc.,?for sharing mutation classification and frequency data. This study was supported by NIH grants U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24?CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, and P30 CA016672. S.L.A. is part of the pathology imaging medical advisory board of Leica Biosystems. Andrew D. Cherniack and Matthew Meyerson received research support from Bayer AG. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = feb,

day = "13",

doi = "10.1016/j.ccell.2017.01.001",

language = "English",

volume = "31",

pages = "181--193",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "2",

}

Fishbein, L, Leshchiner, I, Walter, V, Danilova, L, Robertson, AG, Johnson, AR, Lichtenberg, TM, Murray, BA, Ghayee, HK, Else, T, Ling, S, Jefferys, SR, de Cubas, AA, Wenz, B, Korpershoek, E, Amelio, AL, Makowski, L, Rathmell, WK, Gimenez-Roqueplo, AP, Giordano, TJ, Asa, SL, Tischler, AS, Akbani, R, Ally, A, Amar, L, Amelio, AL, Arachchi, H, Asa, SL, Auchus, RJ, Auman, JT, Baertsch, R, Balasundaram, M, Balu, S, Bartsch, DK, Baudin, E, Bauer, T, Beaver, A, Benz, C, Beroukhim, R, Beuschlein, F, Bodenheimer, T, Boice, L, Bowen, J, Bowlby, R, Brooks, D, Carlsen, R, Carter, S, Cassol, CA, Cherniack, AD, Chin, L, Cho, J, Chuah, E, Chudamani, S, Cope, L, Crain, D, Curley, E, Danilova, L, de Cubas, AA, de Krijger, RR, Demchok, JA, Deutschbein, T, Dhalla, N, Dimmock, D, Dinjens, WNM, Else, T, Eng, C, Eschbacher, J, Fassnacht, M, Felau, I, Feldman, M, Ferguson, ML, Fiddes, I, Fishbein, L, Frazer, S, Gabriel, SB, Gardner, J, Gastier-Foster, JM, Gehlenborg, N, Gerken, M, Getz, G, Geurts, J, Ghayee, HK, Gimenez-Roqueplo, AP, Giordano, TJ, Goldman, M, Graim, K, Gupta, M, Haan, D, Hahner, S, Hantel, C, Haussler, D, Hayes, DN, Heiman, DI, Hoadley, KA, Holt, RA, Hoyle, AP, Huang, M, Hunt, B, Hutter, CM, Jefferys, SR, Johnson, AR, Jones, SJM, Jones, CD, Kasaian, K, Kebebew, E, Kim, J, Kimes, P, Knijnenburg, T, Korpershoek, E, Lander, E, Lawrence, MS, Lechan, R, Lee, D, Leraas, KM, Lerario, A, Leshchiner, I, Lichtenberg, TM, Lin, P, Ling, S, Liu, J, LiVolsi, VA, Lolla, L, Lotan, Y, Lu, Y, Ma, Y, Maison, N, Makowski, L, Mallery, D, Mannelli, M, Marquard, J, Marra, MA, Matthew, T, Mayo, M, Méatchi, T, Meng, S, Merino, MJ, Mete, O, Meyerson, M, Mieczkowski, PA, Mills, GB, Moore, RA, Morozova, O, Morris, S, Mose, LE, Mungall, AJ, Murray, BA, Naresh, R, Nathanson, KL, Newton, Y, Ng, S, Ni, Y, Noble, MS, Nwariaku, F, Pacak, K, Parker, JS, Paul, E, Penny, R, Perou, CM, Perou, AH, Pihl, T, Powers, J, Rabaglia, J, Radenbaugh, A, Ramirez, NC, Rao, A, Rathmell, WK, Riester, A, Roach, J, Robertson, AG, Sadeghi, S, Saksena, G, Salama, S, Saller, C, Sandusky, G, Sbiera, S, Schein, JE, Schumacher, SE, Shelton, C, Shelton, T, Sheth, M, Shi, Y, Shih, J, Shmulevich, I, Simons, JV, Sipahimalani, P, Skelly, T, Sofia, HJ, Sokolov, A, Soloway, MG, Sougnez, C, Stuart, J, Sun, C, Swatloski, T, Tam, A, Tan, D, Tarnuzzer, R, Tarvin, K, Thiessen, N, Thorne, LB, Timmers, HJ, Tischler, AS, Tse, K, Uzunangelov, V, van Berkel, A, Veluvolu, U, Vicha, A, Voet, D, Waldmann, J, Walter, V, Wan, Y, Wang, Z, Wang, TS, Weaver, J, Weinstein, JN, Weismann, D, Wenz, B, Wilkerson, MD, Wise, L, Wong, T, Wong, C, Wu, Y, Yang, L, Zelinka, T, Zenklusen, JC, Zhang, J, Zhang, W, Zhu, J, Zinzindohoué, F, Zmuda, E, Pacak, K, Nathanson, KL & Wilkerson, MD 2017, 'Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma', Cancer Cell, vol. 31, no. 2, pp. 181-193. https://doi.org/10.1016/j.ccell.2017.01.001

TY - JOUR

T1 - Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

AU - Fishbein, Lauren

AU - Leshchiner, Ignaty

AU - Walter, Vonn

AU - Danilova, Ludmila

AU - Robertson, A. Gordon

AU - Johnson, Amy R.

AU - Lichtenberg, Tara M.

AU - Murray, Bradley A.

AU - Ghayee, Hans K.

AU - Else, Tobias

AU - Ling, Shiyun

AU - Jefferys, Stuart R.

AU - de Cubas, Aguirre A.

AU - Wenz, Brandon

AU - Korpershoek, Esther

AU - Amelio, Antonio L.

AU - Makowski, Liza

AU - Rathmell, W. Kimryn

AU - Gimenez-Roqueplo, Anne Paule

AU - Giordano, Thomas J.

AU - Asa, Sylvia L.

AU - Tischler, Arthur S.

AU - Akbani, Rehan

AU - Ally, Adrian

AU - Amar, Laurence

AU - Amelio, Antonio L.

AU - Arachchi, Harindra

AU - Asa, Sylvia L.

AU - Auchus, Richard J.

AU - Auman, J. Todd

AU - Baertsch, Robert

AU - Balasundaram, Miruna

AU - Balu, Saianand

AU - Bartsch, Detlef K.

AU - Baudin, Eric

AU - Bauer, Thomas

AU - Beaver, Allison

AU - Benz, Christopher

AU - Beroukhim, Rameen

AU - Beuschlein, Felix

AU - Bodenheimer, Tom

AU - Boice, Lori

AU - Bowen, Jay

AU - Bowlby, Reanne

AU - Brooks, Denise

AU - Carlsen, Rebecca

AU - Carter, Suzie

AU - Cassol, Clarissa A.

AU - Cherniack, Andrew D.

AU - Chin, Lynda

AU - Cho, Juok

AU - Chuah, Eric

AU - Chudamani, Sudha

AU - Cope, Leslie

AU - Crain, Daniel

AU - Curley, Erin

AU - Danilova, Ludmila

AU - de Cubas, Aguirre A.

AU - de Krijger, Ronald R.

AU - Demchok, John A.

AU - Deutschbein, Timo

AU - Dhalla, Noreen

AU - Dimmock, David

AU - Dinjens, Winand N M

AU - Else, Tobias

AU - Eng, Charis

AU - Eschbacher, Jennifer

AU - Fassnacht, Martin

AU - Felau, Ina

AU - Feldman, Michael

AU - Ferguson, Martin L.

AU - Fiddes, Ian

AU - Fishbein, Lauren

AU - Frazer, Scott

AU - Gabriel, Stacey B.

AU - Gardner, Johanna

AU - Gastier-Foster, Julie M.

AU - Gehlenborg, Nils

AU - Gerken, Mark

AU - Getz, Gad

AU - Geurts, Jennifer

AU - Ghayee, Hans K.

AU - Gimenez-Roqueplo, Anne Paule

AU - Giordano, Thomas J.

AU - Goldman, Mary

AU - Graim, Kiley

AU - Gupta, Manaswi

AU - Haan, David

AU - Hahner, Stefanie

AU - Hantel, Constanze

AU - Haussler, David

AU - Hayes, D. Neil

AU - Heiman, David I.

AU - Hoadley, Katherine A.

AU - Holt, Robert A.

AU - Hoyle, Alan P.

AU - Huang, Mei

AU - Hunt, Bryan

AU - Hutter, Carolyn M.

AU - Jefferys, Stuart R.

AU - Johnson, Amy R.

AU - Jones, Steven J M

AU - Jones, Corbin D.

AU - Kasaian, Katayoon

AU - Kebebew, Electron

AU - Kim, Jaegil

AU - Kimes, Patrick

AU - Knijnenburg, Theo

AU - Korpershoek, Esther

AU - Lander, Eric

AU - Lawrence, Michael S.

AU - Lechan, Ronald

AU - Lee, Darlene

AU - Leraas, Kristen M.

AU - Lerario, Antonio

AU - Leshchiner, Ignaty

AU - Lichtenberg, Tara M.

AU - Lin, Pei

AU - Ling, Shiyun

AU - Liu, Jia

AU - LiVolsi, Virginia A.

AU - Lolla, Laxmi

AU - Lotan, Yair

AU - Lu, Yiling

AU - Ma, Yussanne

AU - Maison, Nicole

AU - Makowski, Liza

AU - Mallery, David

AU - Mannelli, Massimo

AU - Marquard, Jessica

AU - Marra, Marco A.

AU - Matthew, Thomas

AU - Mayo, Michael

AU - Méatchi, Tchao

AU - Meng, Shaowu

AU - Merino, Maria J.

AU - Mete, Ozgur

AU - Meyerson, Matthew

AU - Mieczkowski, Piotr A.

AU - Mills, Gordon B.

AU - Moore, Richard A.

AU - Morozova, Olena

AU - Morris, Scott

AU - Mose, Lisle E.

AU - Mungall, Andrew J.

AU - Murray, Bradley A.

AU - Naresh, Rashi

AU - Nathanson, Katherine L.

AU - Newton, Yulia

AU - Ng, Sam

AU - Ni, Ying

AU - Noble, Michael S.

AU - Nwariaku, Fiemu

AU - Pacak, Karel

AU - Parker, Joel S.

AU - Paul, Evan

AU - Penny, Robert

AU - Perou, Charles M.

AU - Perou, Amy H.

AU - Pihl, Todd

AU - Powers, James

AU - Rabaglia, Jennifer

AU - Radenbaugh, Amie

AU - Ramirez, Nilsa C.

AU - Rao, Arjun

AU - Rathmell, W. Kimryn

AU - Riester, Anna

AU - Roach, Jeffrey

AU - Robertson, A. Gordon

AU - Sadeghi, Sara

AU - Saksena, Gordon

AU - Salama, Sofie

AU - Saller, Charles

AU - Sandusky, George

AU - Sbiera, Silviu

AU - Schein, Jacqueline E.

AU - Schumacher, Steven E.

AU - Shelton, Candace

AU - Shelton, Troy

AU - Sheth, Margi

AU - Shi, Yan

AU - Shih, Juliann

AU - Shmulevich, Ilya

AU - Simons, Janae V.

AU - Sipahimalani, Payal

AU - Skelly, Tara

AU - Sofia, Heidi J.

AU - Sokolov, Artem

AU - Soloway, Matthew G.

AU - Sougnez, Carrie

AU - Stuart, Josh

AU - Sun, Charlie

AU - Swatloski, Teresa

AU - Tam, Angela

AU - Tan, Donghui

AU - Tarnuzzer, Roy

AU - Tarvin, Katherine

AU - Thiessen, Nina

AU - Thorne, Leigh B.

AU - Timmers, Henri J.

AU - Tischler, Arthur S.

AU - Tse, Kane

AU - Uzunangelov, Vlado

AU - van Berkel, Anouk

AU - Veluvolu, Umadevi

AU - Vicha, Ales

AU - Voet, Doug

AU - Waldmann, Jens

AU - Walter, Vonn

AU - Wan, Yunhu

AU - Wang, Zhining

AU - Wang, Tracy S.

AU - Weaver, Joellen

AU - Weinstein, John N.

AU - Weismann, Dirk

AU - Wenz, Brandon

AU - Wilkerson, Matthew D.

AU - Wise, Lisa

AU - Wong, Tina

AU - Wong, Christopher

AU - Wu, Ye

AU - Yang, Liming

AU - Zelinka, Tomas

AU - Zenklusen, Jean C.

AU - Zhang, Jiashan (Julia)

AU - Zhang, Wei

AU - Zhu, Jingchun

AU - Zinzindohoué, Franck

AU - Zmuda, Erik

AU - Pacak, Karel

AU - Nathanson, Katherine L.

AU - Wilkerson, Matthew D.

N1 - Funding Information: We thank all of the patients and families who contributed to the study, Ina Felau for project management, and Jill Dolinsky, MS, CGC, at Ambry Genetics, Inc.,?for sharing mutation classification and frequency data. This study was supported by NIH grants U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24?CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, and P30 CA016672. S.L.A. is part of the pathology imaging medical advisory board of Leica Biosystems. Andrew D. Cherniack and Matthew Meyerson received research support from Bayer AG. Publisher Copyright: © 2017 Elsevier Inc.

PY - 2017/2/13

Y1 - 2017/2/13

N2 - We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.

AB - We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.

KW - CSDE1

KW - expression subtypes

KW - genomics

KW - MAML3

KW - metastasis

KW - molecular profiling

KW - paraganglioma

KW - pheochromocytoma

KW - sequencing

KW - TCGA

UR - http://www.scopus.com/inward/record.url?scp=85011305911&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2017.01.001

DO - 10.1016/j.ccell.2017.01.001

M3 - Article

C2 - 28162975

AN - SCOPUS:85011305911

SN - 1535-6108

VL - 31

SP - 181

EP - 193

JO - Cancer Cell

JF - Cancer Cell

IS - 2

ER -

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this