Mutations in the RAS/MAPK Pathway Drive Replication Repair-Deficient Hypermutated Tumors and Confer Sensitivity to MEK Inhibition

被引：31

作者：

Campbell, Brittany B. ^{[1
,2
]}

Galati, Melissa A. ^{[1
,2
]}

Stone, Simone C. ^{[3
]}

Riemenschneider, Alexandra N. ^{[2
,4
]}

Edwards, Melissa ^{[1
,2
]}

Sudhaman, Sumedha ^{[1
,2
,3
]}

Siddaway, Robert ^{[2
,5
]}

Komosa, Martin ^{[1
,2
]}

Nunes, Nuno M. ^{[1
,2
]}

Nobre, Liana ^{[1
,2
]}

Morrissy, A. Sorana ^{[6
]}

Zatzman, Matthew ^{[1
,7
]}

Zapotocky, Michal ^{[2
,8
,9
,10
]}

Joksimovic, Lazar ^{[1
,2
]}

Kalimuthu, Sangeetha N. ^{[11
,12
]}

Samuel, David ^{[13
]}

Mason, Gary ^{[14
]}

Bouffet, Eric ^{[8
]}

Morgenstern, Daniel A. ^{[8
]}

Aronson, Melyssa ^{[15
]}

Durno, Carol ^{[15
]}

Malkin, David ^{[1
,8
]}

Maris, John M. ^{[16
,17
,18
]}

Taylor, Michael D. ^{[2
,4
,19
]}

Shlien, Adam ^{[1
,7
]}

Pugh, Trevor J. ^{[3
,20
,21
]}

Ohashi, Pamela S. ^{[3
,22
]}

Hawkins, Cynthia E. ^{[2
,5
,7
]}

Tabori, Uri ^{[1
,2
,3
]}

机构：

[1] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON, Canada

[2] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada

[3] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[4] Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada

[5] Hosp Sick Children, Program Cell Biol, Toronto, ON, Canada

[6] Univ Calgary, Charbonneau Canc Inst, Calgary, AB, Canada

[7] Univ Toronto, Fac Med, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[8] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Hematol Oncol, Toronto, ON, Canada

[9] Charles Univ Prague, Fac Med 2, Prague, Czech Republic

[10] Univ Hosp Motol, Prague, Czech Republic

[11] Univ Hlth Network, Dept Pathol, Lab Med Program, Toronto, ON, Canada

[12] Univ Toronto, Toronto, ON, Canada

[13] Valley Childrens Hosp, Dept Hematol Oncol, Madera, CA USA

[14] Childrens Hosp Pittsburgh UPMC, Dept Pediat Hematol Oncol, Pittsburgh, PA USA

[15] Mt Sinai Hosp, Zane Cohen Ctr Digest Dis, Toronto, ON, Canada

[16] Univ Penn, Div Oncol, Philadelphia, PA 19104 USA

[17] Univ Penn, Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA

[18] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[19] Hosp Sick Children, Div Neurosurg, Toronto, ON, Canada

[20] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[21] Ontario Inst Canc Res, Toronto, ON, Canada

[22] Univ Toronto, Dept Immunol, Toronto, ON, Canada

来源：

CANCER DISCOVERY | 2021年 / 11卷 / 06期

关键词：

GERMLINE MUTATIONS; SOMATIC MUTATIONS; MSH6; MUTATIONS; CELL-CARCINOMA; PD-1; BLOCKADE; CANCER; SIGNATURES; POLE; GLIOBLASTOMA; SELUMETINIB;

D O I：

10.1158/2159-8290.CD-20-1050

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The RAS/MAPK pathway is an emerging targeted pathway across a spectrum of both adult and pediatric cancers. Typically, this is associated with a single, well-characterized point mutation in an oncogene. Hypermutant tumors that harbor many somatic mutations may obscure the interpretation of such targetable genomic events. We find that replication repair-deficient (RRD) cancers, which are universally hypermutant and affect children born with RRD cancer predisposition, are enriched for RAS/MAPK mutations (P = 10(-8)). These mutations are not random, exist in subclones, and increase in allelic frequency over time. The RAS/MAPK pathway is activated both transcriptionally and at the protein level in patient-derived RRD tumors, and these tumors responded to MEK inhibition in vitro and in vivo. Treatment of patients with RAS/MAPK hypermutant gliomas reveals durable responses to MEK inhibition. Our observations suggest that hypermutant tumors may be addicted to oncogenic pathways, resulting in favorable response to targeted therapies. SIGNIFICANCE: Tumors harboring a single RAS/MAPK driver mutation are targeted individually for therapeutic purposes. We find that in RRD hypermutant cancers, mutations in the RAS/MAPK pathway are enriched, highly expressed, and result in sensitivity to MEK inhibitors. Targeting an oncogenic pathway may provide therapeutic options for these hypermutant polyclonal cancers.

引用

页码：1454 / 1467

页数：14

共 60 条

[1]

Adzhubei Ivan, 2013, Curr Protoc Hum Genet, VChapter 7, DOI 10.1002/0471142905.hg0720s76

[2] Genomic Classification of Cutaneous Melanoma [J].

Akbani, Rehan ;

Akdemir, Kadir C. ;

Aksoy, B. Arman ;

Albert, Monique ;

Ally, Adrian ;

Amin, Samirkumar B. ;

Arachchi, Harindra ;

Arora, Arshi ;

Auman, J. Todd ;

Ayala, Brenda ;

Baboud, Julien ;

Balasundaram, Miruna ;

Balu, Saianand ;

Barnabas, Nandita ;

Bartlett, John ;

Bartlett, Pam ;

Bastian, Boris C. ;

Baylin, Stephen B. ;

Behera, Madhusmita ;

Belyaev, Dmitry ;

Benz, Christopher ;

Bernard, Brady ;

Beroukhim, Rameen ;

Bir, Natalie ;

Black, Aaron D. ;

Bodenheimer, Tom ;

Boice, Lori ;

Boland, Genevieve M. ;

Bono, Riccardo ;

Bootwalla, Moiz S. ;

Bosenberg, Marcus ;

Bowen, Jay ;

Bowlby, Reanne ;

Bristow, Christopher A. ;

Brockway-Lunardi, Laura ;

Brooks, Denise ;

Brzezinski, Jakub ;

Bshara, Wiam ;

Buda, Elizabeth ;

Burns, William R. ;

Butterfield, Yaron S. N. ;

Button, Michael ;

Calderone, Tiffany ;

Cappellini, Giancarlo Antonini ;

Carter, Candace ;

Carter, Scott L. ;

Cherney, Lynn ;

Cherniack, Andrew D. ;

Chevalier, Aaron ;

Chin, Lynda .

CELL, 2015, 161 (07) :1681-1696

[3] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[4] MEK1/2 Inhibitor Selumetinib (AZD6244) Inhibits Growth of Ovarian Clear Cell Carcinoma in a PEA-15-Dependent Manner in a Mouse Xenograft Model [J].

Bartholomeusz, Chandra ;

Oishi, Tetsuro ;

Saso, Hitomi ;

Akar, Ugur ;

Liu, Ping ;

Kondo, Kimie ;

Kazansky, Anna ;

Krishnamurthy, Savitri ;

Lee, Jangsoon ;

Esteva, Francisco J. ;

Kigawa, Junzo ;

Ueno, Naoto T. .

MOLECULAR CANCER THERAPEUTICS, 2012, 11 (02) :360-369

[5] Cancer Risks Associated With Germline Mutations in MLH1, MSH2, and MSH6 Genes in Lynch Syndrome [J].

Bonadona, Valerie ;

Bonaiti, Bernard ;

Olschwang, Sylviane ;

Grandjouan, Sophie ;

Huiart, Laetitia ;

Longy, Michel ;

Guimbaud, Rosine ;

Buecher, Bruno ;

Bignon, Yves-Jean ;

Caron, Olivier ;

Colas, Chrystelle ;

Nogues, Catherine ;

Lejeune-Dumoulin, Sophie ;

Olivier-Faivre, Laurence ;

Polycarpe-Osaer, Florence ;

Nguyen, Tan Dat ;

Desseigne, Francoise ;

Saurin, Jean-Christophe ;

Berthet, Pascaline ;

Leroux, Dominique ;

Duffour, Jacqueline ;

Manouvrier, Sylvie ;

Frebourg, Thierry ;

Sobol, Hagay ;

Lasset, Christine ;

Bonaiti-Pellie, Catherine .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2011, 305 (22) :2304-2310

[6] Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency [J].

Bouffet, Eric ;

Larouche, Valerie ;

Campbell, Brittany B. ;

Merico, Daniele ;

de Borja, Richard ;

Aronson, Melyssa ;

Durno, Carol ;

Krueger, Joerg ;

Cabric, Vanja ;

Ramaswamy, Vijay ;

Zhukova, Nataliya ;

Mason, Gary ;

Farah, Roula ;

Afzal, Samina ;

Yalon, Michal ;

Rechavi, Gideon ;

Magimairajan, Vanan ;

Walsh, Michael F. ;

Constantini, Shlomi ;

Dvir, Rina ;

Elhasid, Ronit ;

Reddy, Alyssa ;

Osborn, Michael ;

Sullivan, Michael ;

Hansford, Jordan ;

Dodgshun, Andrew ;

Klauber-Demore, Nancy ;

Peterson, Lindsay ;

Patel, Sunil ;

Lindhorst, Scott ;

Atkinson, Jeffrey ;

Cohen, Zane ;

Laframboise, Rachel ;

Dirks, Peter ;

Taylor, Michael ;

Malkin, David ;

Albrecht, Steffen ;

Dudley, Roy W. R. ;

Jabado, Nada ;

Hawkins, Cynthia E. ;

Shlien, Adam ;

Tabori, Uri .

JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (19) :2206-+

[7] Comprehensive Analysis of Hypermutation in Human Cancer [J].

Campbell, Brittany B. ;

Light, Nicholas ;

Fabrizio, David ;

Zatzman, Matthew ;

Fuligni, Fabio ;

de Borja, Richard ;

Davidson, Scott ;

Edwards, Melissa ;

Elvin, Julia A. ;

Hodel, Karl P. ;

Zahurancik, Walter J. ;

Suo, Zucai ;

Lipman, Tatiana ;

Wimmer, Katharina ;

Kratz, Christian P. ;

Bowers, Daniel C. ;

Laetsch, Theodore W. ;

Dunn, Gavin P. ;

Johanns, Tanner M. ;

Grimmer, Matthew R. ;

Smirnov, Ivan V. ;

Larouche, Valerie ;

Samuel, David ;

Bronsema, Annika ;

Osborn, Michael ;

Stearns, Duncan ;

Raman, Pichai ;

Cole, Kristina A. ;

Storm, Phillip B. ;

Yalon, Michal ;

Opocher, Enrico ;

Mason, Gary ;

Thomas, Gregory A. ;

Sabel, Magnus ;

George, Ben ;

Ziegler, David S. ;

Lindhorst, Scott ;

Issai, Vanan Magimairajan ;

Constantini, Shlomi ;

Toledano, Helen ;

Elhasid, Ronit ;

Farah, Roula ;

Dvir, Rina ;

Dirks, Peter ;

Huang, Annie ;

Galati, Melissa A. ;

Chung, Jiil ;

Ramaswamy, Vijay ;

Irwin, Meredith S. ;

Aronson, Melyssa .

CELL, 2017, 171 (05) :1042-+

[8] CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells [J].

Canale, Fernando P. ;

Ramello, Maria C. ;

Nunez, Nicolas ;

Furlan, Cintia L. Araujo ;

Bossio, Sabrina N. ;

Serran, Melisa Gorosito ;

Boari, Jimena Tosello ;

del Castillo, Andres ;

Ledesma, Marta ;

Sedlik, Christine ;

Piaggio, Eliane ;

Gruppi, Adriana ;

Rodriguez, Eva V. Acosta ;

Montes, Carolina L. .

CANCER RESEARCH, 2018, 78 (01) :115-128

[9] Accelerating Discovery of Functional Mutant Alleles in Cancer [J].

Chang, Matthew T. ;

Bhattarai, Tripti Shrestha ;

Schram, Alison M. ;

Bielski, Craig M. ;

Donoghue, Mark T. A. ;

Jonsson, Philip ;

Chakravarty, Debyani ;

Phillips, Sarah ;

Kandoth, Cyriac ;

Penson, Alexander ;

Gorelick, Alexander ;

Shamu, Tambudzai ;

Patel, Swati ;

Harris, Christopher ;

Gao, JianJiong ;

Sumer, Selcuk Onur ;

Kundra, Ritika ;

Razavi, Pedram ;

Li, Bob T. ;

Reales, Dalicia N. ;

Socci, Nicholas D. ;

Jayakumaran, Gowtham ;

Zehir, Ahmet ;

Benayed, Ryma ;

Arcila, Maria E. ;

Chandarlapaty, Sarat ;

Ladanyi, Marc ;

Schultz, Nikolaus ;

Baselga, Jose ;

Berger, Michael F. ;

Rosen, Neal ;

Solit, David B. ;

Hyman, David M. ;

Taylor, Barry S. .

CANCER DISCOVERY, 2018, 8 (02) :174-183

[10] The molecular landscape of glioma in patients with Neurofibromatosis 1 [J].

D'Angelo, Fulvio ;

Ceccarelli, Michele ;

Tala ;

Garofano, Luciano ;

Zhang, Jing ;

Frattini, Veronique ;

Caruso, Francesca P. ;

Lewis, Genevieve ;

Alfaro, Kristin D. ;

Bauchet, Luc ;

Berzero, Giulia ;

Cachia, David ;

Cangiano, Mario ;

Capelle, Laurent ;

de Groot, John ;

DiMeco, Francesco ;

Ducray, Francois ;

Farah, Walid ;

Finocchiaro, Gaetano ;

Goutagny, Stephane ;

Kamiya-Matsuoka, Carlos ;

Lavarino, Cinzia ;

Loiseau, Hugues ;

Lorgis, Veronique ;

Marras, Carlo E. ;

McCutcheon, Ian ;

Nam, Do-Hyun ;

Ronchi, Susanna ;

Saletti, Veronica ;

Seizeur, Romuald ;

Slopis, John ;

Sunol, Mariona ;

Vandenbos, Fanny ;

Varlet, Pascale ;

Vidaud, Dominique ;

Watts, Colin ;

Tabar, Viviane ;

Reuss, David E. ;

Kim, Seung-Ki ;

Meyronet, David ;

Mokhtari, Karima ;

Salvador, Hector ;

Bhat, Krishna P. ;

Eoli, Marica ;

Sanson, Marc ;

Lasorella, Anna ;

Iavarone, Antonio .

NATURE MEDICINE, 2019, 25 (01) :176-+

← 1 2 3 4 5 6 →

共 60 条

[1]

Adzhubei Ivan, 2013, Curr Protoc Hum Genet, VChapter 7, DOI 10.1002/0471142905.hg0720s76

[2] Genomic Classification of Cutaneous Melanoma [J].

Akbani, Rehan ;

Akdemir, Kadir C. ;

Aksoy, B. Arman ;

Albert, Monique ;

Ally, Adrian ;

Amin, Samirkumar B. ;

Arachchi, Harindra ;

Arora, Arshi ;

Auman, J. Todd ;

Ayala, Brenda ;

Baboud, Julien ;

Balasundaram, Miruna ;

Balu, Saianand ;

Barnabas, Nandita ;

Bartlett, John ;

Bartlett, Pam ;

Bastian, Boris C. ;

Baylin, Stephen B. ;

Behera, Madhusmita ;

Belyaev, Dmitry ;

Benz, Christopher ;

Bernard, Brady ;

Beroukhim, Rameen ;

Bir, Natalie ;

Black, Aaron D. ;

Bodenheimer, Tom ;

Boice, Lori ;

Boland, Genevieve M. ;

Bono, Riccardo ;

Bootwalla, Moiz S. ;

Bosenberg, Marcus ;

Bowen, Jay ;

Bowlby, Reanne ;

Bristow, Christopher A. ;

Brockway-Lunardi, Laura ;

Brooks, Denise ;

Brzezinski, Jakub ;

Bshara, Wiam ;

Buda, Elizabeth ;

Burns, William R. ;

Butterfield, Yaron S. N. ;

Button, Michael ;

Calderone, Tiffany ;

Cappellini, Giancarlo Antonini ;

Carter, Candace ;

Carter, Scott L. ;

Cherney, Lynn ;

Cherniack, Andrew D. ;

Chevalier, Aaron ;

Chin, Lynda .

CELL, 2015, 161 (07) :1681-1696

[3] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[4] MEK1/2 Inhibitor Selumetinib (AZD6244) Inhibits Growth of Ovarian Clear Cell Carcinoma in a PEA-15-Dependent Manner in a Mouse Xenograft Model [J].

Bartholomeusz, Chandra ;

Oishi, Tetsuro ;

Saso, Hitomi ;

Akar, Ugur ;

Liu, Ping ;

Kondo, Kimie ;

Kazansky, Anna ;

Krishnamurthy, Savitri ;

Lee, Jangsoon ;

Esteva, Francisco J. ;

Kigawa, Junzo ;

Ueno, Naoto T. .

MOLECULAR CANCER THERAPEUTICS, 2012, 11 (02) :360-369

[5] Cancer Risks Associated With Germline Mutations in MLH1, MSH2, and MSH6 Genes in Lynch Syndrome [J].

Bonadona, Valerie ;

Bonaiti, Bernard ;

Olschwang, Sylviane ;

Grandjouan, Sophie ;

Huiart, Laetitia ;

Longy, Michel ;

Guimbaud, Rosine ;

Buecher, Bruno ;

Bignon, Yves-Jean ;

Caron, Olivier ;

Colas, Chrystelle ;

Nogues, Catherine ;

Lejeune-Dumoulin, Sophie ;

Olivier-Faivre, Laurence ;

Polycarpe-Osaer, Florence ;

Nguyen, Tan Dat ;

Desseigne, Francoise ;

Saurin, Jean-Christophe ;

Berthet, Pascaline ;

Leroux, Dominique ;

Duffour, Jacqueline ;

Manouvrier, Sylvie ;

Frebourg, Thierry ;

Sobol, Hagay ;

Lasset, Christine ;

Bonaiti-Pellie, Catherine .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2011, 305 (22) :2304-2310

[6] Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency [J].

Bouffet, Eric ;

Larouche, Valerie ;

Campbell, Brittany B. ;

Merico, Daniele ;

de Borja, Richard ;

Aronson, Melyssa ;

Durno, Carol ;

Krueger, Joerg ;

Cabric, Vanja ;

Ramaswamy, Vijay ;

Zhukova, Nataliya ;

Mason, Gary ;

Farah, Roula ;

Afzal, Samina ;

Yalon, Michal ;

Rechavi, Gideon ;

Magimairajan, Vanan ;

Walsh, Michael F. ;

Constantini, Shlomi ;

Dvir, Rina ;

Elhasid, Ronit ;

Reddy, Alyssa ;

Osborn, Michael ;

Sullivan, Michael ;

Hansford, Jordan ;

Dodgshun, Andrew ;

Klauber-Demore, Nancy ;

Peterson, Lindsay ;

Patel, Sunil ;

Lindhorst, Scott ;

Atkinson, Jeffrey ;

Cohen, Zane ;

Laframboise, Rachel ;

Dirks, Peter ;

Taylor, Michael ;

Malkin, David ;

Albrecht, Steffen ;

Dudley, Roy W. R. ;

Jabado, Nada ;

Hawkins, Cynthia E. ;

Shlien, Adam ;

Tabori, Uri .

JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (19) :2206-+

[7] Comprehensive Analysis of Hypermutation in Human Cancer [J].

Campbell, Brittany B. ;

Light, Nicholas ;

Fabrizio, David ;

Zatzman, Matthew ;

Fuligni, Fabio ;

de Borja, Richard ;

Davidson, Scott ;

Edwards, Melissa ;

Elvin, Julia A. ;

Hodel, Karl P. ;

Zahurancik, Walter J. ;

Suo, Zucai ;

Lipman, Tatiana ;

Wimmer, Katharina ;

Kratz, Christian P. ;

Bowers, Daniel C. ;

Laetsch, Theodore W. ;

Dunn, Gavin P. ;

Johanns, Tanner M. ;

Grimmer, Matthew R. ;

Smirnov, Ivan V. ;

Larouche, Valerie ;

Samuel, David ;

Bronsema, Annika ;

Osborn, Michael ;

Stearns, Duncan ;

Raman, Pichai ;

Cole, Kristina A. ;

Storm, Phillip B. ;

Yalon, Michal ;

Opocher, Enrico ;

Mason, Gary ;

Thomas, Gregory A. ;

Sabel, Magnus ;

George, Ben ;

Ziegler, David S. ;

Lindhorst, Scott ;

Issai, Vanan Magimairajan ;

Constantini, Shlomi ;

Toledano, Helen ;

Elhasid, Ronit ;

Farah, Roula ;

Dvir, Rina ;

Dirks, Peter ;

Huang, Annie ;

Galati, Melissa A. ;

Chung, Jiil ;

Ramaswamy, Vijay ;

Irwin, Meredith S. ;

Aronson, Melyssa .

CELL, 2017, 171 (05) :1042-+

[8] CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells [J].

Canale, Fernando P. ;

Ramello, Maria C. ;

Nunez, Nicolas ;

Furlan, Cintia L. Araujo ;

Bossio, Sabrina N. ;

Serran, Melisa Gorosito ;

Boari, Jimena Tosello ;

del Castillo, Andres ;

Ledesma, Marta ;

Sedlik, Christine ;

Piaggio, Eliane ;

Gruppi, Adriana ;

Rodriguez, Eva V. Acosta ;

Montes, Carolina L. .

CANCER RESEARCH, 2018, 78 (01) :115-128

[9] Accelerating Discovery of Functional Mutant Alleles in Cancer [J].

Chang, Matthew T. ;

Bhattarai, Tripti Shrestha ;

Schram, Alison M. ;

Bielski, Craig M. ;

Donoghue, Mark T. A. ;

Jonsson, Philip ;

Chakravarty, Debyani ;

Phillips, Sarah ;

Kandoth, Cyriac ;

Penson, Alexander ;

Gorelick, Alexander ;

Shamu, Tambudzai ;

Patel, Swati ;

Harris, Christopher ;

Gao, JianJiong ;

Sumer, Selcuk Onur ;

Kundra, Ritika ;

Razavi, Pedram ;

Li, Bob T. ;

Reales, Dalicia N. ;

Socci, Nicholas D. ;

Jayakumaran, Gowtham ;

Zehir, Ahmet ;

Benayed, Ryma ;

Arcila, Maria E. ;

Chandarlapaty, Sarat ;

Ladanyi, Marc ;

Schultz, Nikolaus ;

Baselga, Jose ;

Berger, Michael F. ;

Rosen, Neal ;

Solit, David B. ;

Hyman, David M. ;

Taylor, Barry S. .

CANCER DISCOVERY, 2018, 8 (02) :174-183

[10] The molecular landscape of glioma in patients with Neurofibromatosis 1 [J].

D'Angelo, Fulvio ;

Ceccarelli, Michele ;

Tala ;

Garofano, Luciano ;

Zhang, Jing ;

Frattini, Veronique ;

Caruso, Francesca P. ;

Lewis, Genevieve ;

Alfaro, Kristin D. ;

Bauchet, Luc ;

Berzero, Giulia ;

Cachia, David ;

Cangiano, Mario ;

Capelle, Laurent ;

de Groot, John ;

DiMeco, Francesco ;

Ducray, Francois ;

Farah, Walid ;

Finocchiaro, Gaetano ;

Goutagny, Stephane ;

Kamiya-Matsuoka, Carlos ;

Lavarino, Cinzia ;

Loiseau, Hugues ;

Lorgis, Veronique ;

Marras, Carlo E. ;

McCutcheon, Ian ;

Nam, Do-Hyun ;

Ronchi, Susanna ;

Saletti, Veronica ;

Seizeur, Romuald ;

Slopis, John ;

Sunol, Mariona ;

Vandenbos, Fanny ;

Varlet, Pascale ;

Vidaud, Dominique ;

Watts, Colin ;

Tabar, Viviane ;

Reuss, David E. ;

Kim, Seung-Ki ;

Meyronet, David ;

Mokhtari, Karima ;

Salvador, Hector ;

Bhat, Krishna P. ;

Eoli, Marica ;

Sanson, Marc ;

Lasorella, Anna ;

Iavarone, Antonio .

NATURE MEDICINE, 2019, 25 (01) :176-+

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