Divergent clonal selection dominates medulloblastoma at recurrence
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MORRISSY, A. Sorana; Livia GARZIA; J.H. David SHIH; Scott ZUYDERDUYN; Xi HUANG; Patryk SKOWRON; Marc REMKE; Florence M.G. CAVALLI; Vijay RAMASWAMY; Patricia E. LINDSAY; Salomeh JELVEH; Laura K. DONOVAN; Xin WANG; Betty LUU; Kory ZAYNE; Yisu LI; Chelsea MAYOH; Nina THIESSEN; Eloi MERCIER; Karen L. MUNGALL; Yusanne MA; Kane TSE; Thomas ZENG; Karey SHUMANSKY; Andrew J.L. ROTH; Sohrab SHAH; Hamza FAROOQ; Noriyuki KIJIMA; Borja L. HOLGADO; John J.Y. LEE; Stuart MATAN-LITHWICK; Jessica LIU; Stephen C. MACK; Alex MANNO; K.A. MICHEALRAJ; Carolina NOR; John PEACOCK; Lei QIN; Juri REIMAND; Adi ROLIDER; Yuan Y. THOMPSON; Xiaochong WU; Trevor PUGH; Adrian ALLY; Mikhail BILENKY; Yaron S.N. BUTTERFIELD; Rebecca CARLSEN; Young CHENG; Eric CHUAH; Richard D. CORBETT; Noreen DHALLA; An HE; Darlene LEE; Haiyan I. LI; William LONG; Michael MAYO; Patrick PLETTNER; Jenny Q. QIAN; Jacqueline E. SCHEIN; Angela TAM; Tina WONG; Inanc BIROL; Yongjun ZHAO; Claudia C. FARIA; José PIMENTEL; Sofia NUNES; Tarek SHALABY; Michael GROTZER; Ian F. POLLACK; Ronald L. HAMILTON; Xiao-Nan LI; Anne E. BENDEL; Daniel W. FULTS; Andrew W. WALTER; Toshihiro KUMABE; Teiji TOMINAGA; V. Peter COLLINS; Yoon-Jae CHO; Caitlin HOFFMAN; David LYDEN; Jeffrey H. WISOFF; James H. GARVIN JR; Duncan S. STEARNS; Luca MASSIMI; Ulrich SCHÜLLER; Jaroslav ŠTĚRBA; Karel ZITTERBART; Stephanie PUGET; Olivier AYRAULT; Sandra E. DUNN; Daniela P.C. TIRAPELLI; Carlos G. CARLOTTI; Helen WHEELER; Andrew R. HALLAHAN; Wendy INGRAM; Tobey J. MACDONALD; Jeffrey J. OLSON; Erwin G. Van MEIR; Ji-Yeoun LEE; Kyu-Chang WANG; Seung-Ki KIM; Byung-Kyu CHO; Torsten PIETSCH; Gudrun FLEISCHHACK; Stephan TIPPELT; Young Shin RA; Simon BAILEY; Janet C. LINDSEY; Steven C. CLIFFORD; Charles G. EBERHART; Michael K. COOPER; Roger J. PACKER; Maura MASSIMINO; Maria Luisa GARRE; Ute BARTELS; Uri TABORI; Cynthia E. HAWKINS; Peter DIRKS; Eric BOUFFET; James T. RUTKA; Robert J. WECHSLER-REYA; William A. WEISS; Lara S. COLLIER; Adam J. DUPUY; Andrey KORSHUNOV; David T.W. JONES; Marcel KOOL; Paul A. NORTHCOTT; Stefan M. PFISTER; David A. LARGAESPADA; Andrew J. MUNGALL; Richard A. MOORE; Nada JABADO; Gary D. BADER; Steven J.M. JONES; David MALKIN; Marco A. MARRA a Michael D. TAYLOR
The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.
MORRISSY, A. Sorana; Livia GARZIA; J.H. David SHIH; Scott ZUYDERDUYN; Xi HUANG; Patryk SKOWRON; Marc REMKE; Florence M.G. CAVALLI; Vijay RAMASWAMY; Patricia E. LINDSAY; Salomeh JELVEH; Laura K. DONOVAN; Xin WANG; Betty LUU; Kory ZAYNE; Yisu LI; Chelsea MAYOH; Nina THIESSEN; Eloi MERCIER; Karen L. MUNGALL; Yusanne MA; Kane TSE; Thomas ZENG; Karey SHUMANSKY; Andrew J.L. ROTH; Sohrab SHAH; Hamza FAROOQ; Noriyuki KIJIMA; Borja L. HOLGADO; John J.Y. LEE; Stuart MATAN-LITHWICK; Jessica LIU; Stephen C. MACK; Alex MANNO; K.A. MICHEALRAJ; Carolina NOR; John PEACOCK; Lei QIN; Juri REIMAND; Adi ROLIDER; Yuan Y. THOMPSON; Xiaochong WU; Trevor PUGH; Adrian ALLY; Mikhail BILENKY; Yaron S.N. BUTTERFIELD; Rebecca CARLSEN; Young CHENG; Eric CHUAH; Richard D. CORBETT; Noreen DHALLA; An HE; Darlene LEE; Haiyan I. LI; William LONG; Michael MAYO; Patrick PLETTNER; Jenny Q. QIAN; Jacqueline E. SCHEIN; Angela TAM; Tina WONG; Inanc BIROL; Yongjun ZHAO; Claudia C. FARIA; José PIMENTEL; Sofia NUNES; Tarek SHALABY; Michael GROTZER; Ian F. POLLACK; Ronald L. HAMILTON; Xiao-Nan LI; Anne E. BENDEL; Daniel W. FULTS; Andrew W. WALTER; Toshihiro KUMABE; Teiji TOMINAGA; V. Peter COLLINS; Yoon-Jae CHO; Caitlin HOFFMAN; David LYDEN; Jeffrey H. WISOFF; James H. GARVIN JR; Duncan S. STEARNS; Luca MASSIMI; Ulrich SCHÜLLER; Jaroslav ŠTĚRBA; Karel ZITTERBART; Stephanie PUGET; Olivier AYRAULT; Sandra E. DUNN; Daniela P.C. TIRAPELLI; Carlos G. CARLOTTI; Helen WHEELER; Andrew R. HALLAHAN; Wendy INGRAM; Tobey J. MACDONALD; Jeffrey J. OLSON; Erwin G. Van MEIR; Ji-Yeoun LEE; Kyu-Chang WANG; Seung-Ki KIM; Byung-Kyu CHO; Torsten PIETSCH; Gudrun FLEISCHHACK; Stephan TIPPELT; Young Shin RA; Simon BAILEY; Janet C. LINDSEY; Steven C. CLIFFORD; Charles G. EBERHART; Michael K. COOPER; Roger J. PACKER; Maura MASSIMINO; Maria Luisa GARRE; Ute BARTELS; Uri TABORI; Cynthia E. HAWKINS; Peter DIRKS; Eric BOUFFET; James T. RUTKA; Robert J. WECHSLER-REYA; William A. WEISS; Lara S. COLLIER; Adam J. DUPUY; Andrey KORSHUNOV; David T.W. JONES; Marcel KOOL; Paul A. NORTHCOTT; Stefan M. PFISTER; David A. LARGAESPADA; Andrew J. MUNGALL; Richard A. MOORE; Nada JABADO; Gary D. BADER; Steven J.M. JONES; David MALKIN; Marco A. MARRA a Michael D. TAYLOR. Divergent clonal selection dominates medulloblastoma at recurrence. Nature. London: Nature Publishing Group, 2016, roč. 529, č. 7586, s. 351-371. ISSN 0028-0836. Dostupné z: https://doi.org/10.1038/nature16478.
@article{1362957, author = {Morrissy, A. Sorana and Garzia, Livia and Shih, J.H. David and Zuyderduyn, Scott and Huang, Xi and Skowron, Patryk and Remke, Marc and Cavalli, Florence M.G. and Ramaswamy, Vijay and Lindsay, Patricia E. and Jelveh, Salomeh and Donovan, Laura K. and Wang, Xin and Luu, Betty and Zayne, Kory and Li, Yisu and Mayoh, Chelsea and Thiessen, Nina and Mercier, Eloi and Mungall, Karen L. and Ma, Yusanne and Tse, Kane and Zeng, Thomas and Shumansky, Karey and Roth, Andrew J.L. and Shah, Sohrab and Farooq, Hamza and Kijima, Noriyuki and Holgado, Borja L. and Lee, John J.Y. and MatanandLithwick, Stuart and Liu, Jessica and Mack, Stephen C. and Manno, Alex and Michealraj, K.A. and Nor, Carolina and Peacock, John and Qin, Lei and Reimand, Juri and Rolider, Adi and Thompson, Yuan Y. and Wu, Xiaochong and Pugh, Trevor and Ally, Adrian and Bilenky, Mikhail and Butterfield, Yaron S.N. and Carlsen, Rebecca and Cheng, Young and Chuah, Eric and Corbett, Richard D. and Dhalla, Noreen and He, An and Lee, Darlene and Li, Haiyan I. and Long, William and Mayo, Michael and Plettner, Patrick and Qian, Jenny Q. and Schein, Jacqueline E. and Tam, Angela and Wong, Tina and Birol, Inanc and Zhao, Yongjun and Faria, Claudia C. and Pimentel, José and Nunes, Sofia and Shalaby, Tarek and Grotzer, Michael and Pollack, Ian F. and Hamilton, Ronald L. and Li, XiaoandNan and Bendel, Anne E. and Fults, Daniel W. and Walter, Andrew W. and Kumabe, Toshihiro and Tominaga, Teiji and Collins, V. Peter and Cho, YoonandJae and Hoffman, Caitlin and Lyden, David and Wisoff, Jeffrey H. and Garvin Jr, James H. and Stearns, Duncan S. and Massimi, Luca and Schüller, Ulrich and Štěrba, Jaroslav and Zitterbart, Karel and Puget, Stephanie and Ayrault, Olivier and Dunn, Sandra E. and Tirapelli, Daniela P.C. and Carlotti, Carlos G. and Wheeler, Helen and Hallahan, Andrew R. and Ingram, Wendy and MacDonald, Tobey J. and Olson, Jeffrey J. and Meir, Erwin G. Van and Lee, JiandYeoun and Wang, KyuandChang and Kim, SeungandKi and Cho, ByungandKyu and Pietsch, Torsten and Fleischhack, Gudrun and Tippelt, Stephan and Ra, Young Shin and Bailey, Simon and Lindsey, Janet C. and Clifford, Steven C. and Eberhart, Charles G. and Cooper, Michael K. and Packer, Roger J. and Massimino, Maura and Garre, Maria Luisa and Bartels, Ute and Tabori, Uri and Hawkins, Cynthia E. and Dirks, Peter and Bouffet, Eric and Rutka, James T. and WechslerandReya, Robert J. and Weiss, William A. and Collier, Lara S. and Dupuy, Adam J. and Korshunov, Andrey and Jones, David T.W. and Kool, Marcel and Northcott, Paul A. and Pfister, Stefan M. and Largaespada, David A. and Mungall, Andrew J. and Moore, Richard A. and Jabado, Nada and Bader, Gary D. and Jones, Steven J.M. and Malkin, David and Marra, Marco A. and Taylor, Michael D.}, article_location = {London}, article_number = {7586}, doi = {https://doi.org/10.1038/nature16478}, keywords = {SUBGROUP MEDULLOBLASTOMA; LYMPHOBLASTIC-LEUKEMIA; CANCER EVOLUTION; SEQUENCING DATA; GENOME; MUTATIONS; HETEROGENEITY; DYNAMICS; IMPACT; CELLS}, language = {eng}, issn = {0028-0836}, journal = {Nature}, title = {Divergent clonal selection dominates medulloblastoma at recurrence}, volume = {529}, year = {2016} }
TY - JOUR ID - 1362957 AU - Morrissy, A. Sorana - Garzia, Livia - Shih, J.H. David - Zuyderduyn, Scott - Huang, Xi - Skowron, Patryk - Remke, Marc - Cavalli, Florence M.G. - Ramaswamy, Vijay - Lindsay, Patricia E. - Jelveh, Salomeh - Donovan, Laura K. - Wang, Xin - Luu, Betty - Zayne, Kory - Li, Yisu - Mayoh, Chelsea - Thiessen, Nina - Mercier, Eloi - Mungall, Karen L. - Ma, Yusanne - Tse, Kane - Zeng, Thomas - Shumansky, Karey - Roth, Andrew J.L. - Shah, Sohrab - Farooq, Hamza - Kijima, Noriyuki - Holgado, Borja L. - Lee, John J.Y. - Matan-Lithwick, Stuart - Liu, Jessica - Mack, Stephen C. - Manno, Alex - Michealraj, K.A. - Nor, Carolina - Peacock, John - Qin, Lei - Reimand, Juri - Rolider, Adi - Thompson, Yuan Y. - Wu, Xiaochong - Pugh, Trevor - Ally, Adrian - Bilenky, Mikhail - Butterfield, Yaron S.N. - Carlsen, Rebecca - Cheng, Young - Chuah, Eric - Corbett, Richard D. - Dhalla, Noreen - He, An - Lee, Darlene - Li, Haiyan I. - Long, William - Mayo, Michael - Plettner, Patrick - Qian, Jenny Q. - Schein, Jacqueline E. - Tam, Angela - Wong, Tina - Birol, Inanc - Zhao, Yongjun - Faria, Claudia C. - Pimentel, José - Nunes, Sofia - Shalaby, Tarek - Grotzer, Michael - Pollack, Ian F. - Hamilton, Ronald L. - Li, Xiao-Nan - Bendel, Anne E. - Fults, Daniel W. - Walter, Andrew W. - Kumabe, Toshihiro - Tominaga, Teiji - Collins, V. Peter - Cho, Yoon-Jae - Hoffman, Caitlin - Lyden, David - Wisoff, Jeffrey H. - Garvin Jr, James H. - Stearns, Duncan S. - Massimi, Luca - Schüller, Ulrich - Štěrba, Jaroslav - Zitterbart, Karel - Puget, Stephanie - Ayrault, Olivier - Dunn, Sandra E. - Tirapelli, Daniela P.C. - Carlotti, Carlos G. - Wheeler, Helen - Hallahan, Andrew R. - Ingram, Wendy - MacDonald, Tobey J. - Olson, Jeffrey J. - Meir, Erwin G. Van - Lee, Ji-Yeoun - Wang, Kyu-Chang - Kim, Seung-Ki - Cho, Byung-Kyu - Pietsch, Torsten - Fleischhack, Gudrun - Tippelt, Stephan - Ra, Young Shin - Bailey, Simon - Lindsey, Janet C. - Clifford, Steven C. - Eberhart, Charles G. - Cooper, Michael K. - Packer, Roger J. - Massimino, Maura - Garre, Maria Luisa - Bartels, Ute - Tabori, Uri - Hawkins, Cynthia E. - Dirks, Peter - Bouffet, Eric - Rutka, James T. - Wechsler-Reya, Robert J. - Weiss, William A. - Collier, Lara S. - Dupuy, Adam J. - Korshunov, Andrey - Jones, David T.W. - Kool, Marcel - Northcott, Paul A. - Pfister, Stefan M. - Largaespada, David A. - Mungall, Andrew J. - Moore, Richard A. - Jabado, Nada - Bader, Gary D. - Jones, Steven J.M. - Malkin, David - Marra, Marco A. - Taylor, Michael D. PY - 2016 TI - Divergent clonal selection dominates medulloblastoma at recurrence JF - Nature VL - 529 IS - 7586 SP - 351-371 EP - 351-371 PB - Nature Publishing Group SN - 00280836 KW - SUBGROUP MEDULLOBLASTOMA KW - LYMPHOBLASTIC-LEUKEMIA KW - CANCER EVOLUTION KW - SEQUENCING DATA KW - GENOME KW - MUTATIONS KW - HETEROGENEITY KW - DYNAMICS KW - IMPACT KW - CELLS N2 - The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy. ER -
MORRISSY, A. Sorana; Livia GARZIA; J.H. David SHIH; Scott ZUYDERDUYN; Xi HUANG; Patryk SKOWRON; Marc REMKE; Florence M.G. CAVALLI; Vijay RAMASWAMY; Patricia E. LINDSAY; Salomeh JELVEH; Laura K. DONOVAN; Xin WANG; Betty LUU; Kory ZAYNE; Yisu LI; Chelsea MAYOH; Nina THIESSEN; Eloi MERCIER; Karen L. MUNGALL; Yusanne MA; Kane TSE; Thomas ZENG; Karey SHUMANSKY; Andrew J.L. ROTH; Sohrab SHAH; Hamza FAROOQ; Noriyuki KIJIMA; Borja L. HOLGADO; John J.Y. LEE; Stuart MATAN-LITHWICK; Jessica LIU; Stephen C. MACK; Alex MANNO; K.A. MICHEALRAJ; Carolina NOR; John PEACOCK; Lei QIN; Juri REIMAND; Adi ROLIDER; Yuan Y. THOMPSON; Xiaochong WU; Trevor PUGH; Adrian ALLY; Mikhail BILENKY; Yaron S.N. BUTTERFIELD; Rebecca CARLSEN; Young CHENG; Eric CHUAH; Richard D. CORBETT; Noreen DHALLA; An HE; Darlene LEE; Haiyan I. LI; William LONG; Michael MAYO; Patrick PLETTNER; Jenny Q. QIAN; Jacqueline E. SCHEIN; Angela TAM; Tina WONG; Inanc BIROL; Yongjun ZHAO; Claudia C. FARIA; José PIMENTEL; Sofia NUNES; Tarek SHALABY; Michael GROTZER; Ian F. POLLACK; Ronald L. HAMILTON; Xiao-Nan LI; Anne E. BENDEL; Daniel W. FULTS; Andrew W. WALTER; Toshihiro KUMABE; Teiji TOMINAGA; V. Peter COLLINS; Yoon-Jae CHO; Caitlin HOFFMAN; David LYDEN; Jeffrey H. WISOFF; James H. GARVIN JR; Duncan S. STEARNS; Luca MASSIMI; Ulrich SCHÜLLER; Jaroslav ŠTĚRBA; Karel ZITTERBART; Stephanie PUGET; Olivier AYRAULT; Sandra E. DUNN; Daniela P.C. TIRAPELLI; Carlos G. CARLOTTI; Helen WHEELER; Andrew R. HALLAHAN; Wendy INGRAM; Tobey J. MACDONALD; Jeffrey J. OLSON; Erwin G. Van MEIR; Ji-Yeoun LEE; Kyu-Chang WANG; Seung-Ki KIM; Byung-Kyu CHO; Torsten PIETSCH; Gudrun FLEISCHHACK; Stephan TIPPELT; Young Shin RA; Simon BAILEY; Janet C. LINDSEY; Steven C. CLIFFORD; Charles G. EBERHART; Michael K. COOPER; Roger J. PACKER; Maura MASSIMINO; Maria Luisa GARRE; Ute BARTELS; Uri TABORI; Cynthia E. HAWKINS; Peter DIRKS; Eric BOUFFET; James T. RUTKA; Robert J. WECHSLER-REYA; William A. WEISS; Lara S. COLLIER; Adam J. DUPUY; Andrey KORSHUNOV; David T.W. JONES; Marcel KOOL; Paul A. NORTHCOTT; Stefan M. PFISTER; David A. LARGAESPADA; Andrew J. MUNGALL; Richard A. MOORE; Nada JABADO; Gary D. BADER; Steven J.M. JONES; David MALKIN; Marco A. MARRA a Michael D. TAYLOR. Divergent clonal selection dominates medulloblastoma at recurrence. \textit{Nature}. London: Nature Publishing Group, 2016, roč.~529, č.~7586, s.~351-371. ISSN~0028-0836. Dostupné z: https://doi.org/10.1038/nature16478.