Divergent clonal selection dominates medulloblastoma at
recurrence

J 2016

Divergent clonal selection dominates medulloblastoma at recurrence

MORRISSY, A. Sorana, Livia GARZIA, J.H. David SHIH, Scott ZUYDERDUYN, Xi HUANG et. al.

Basic information

Original name

Divergent clonal selection dominates medulloblastoma at recurrence

Authors

MORRISSY, A. Sorana (124 Canada), Livia GARZIA (124 Canada), J.H. David SHIH (124 Canada), Scott ZUYDERDUYN (124 Canada), Xi HUANG (124 Canada), Patryk SKOWRON (124 Canada), Marc REMKE (276 Germany), Florence M.G. CAVALLI (124 Canada), Vijay RAMASWAMY (124 Canada), Patricia E. LINDSAY (124 Canada), Salomeh JELVEH (124 Canada), Laura K. DONOVAN (124 Canada), Xin WANG (124 Canada), Betty LUU (124 Canada), Kory ZAYNE (124 Canada), Yisu LI (124 Canada), Chelsea MAYOH (124 Canada), Nina THIESSEN (124 Canada), Eloi MERCIER (124 Canada), Karen L. MUNGALL (124 Canada), Yusanne MA (124 Canada), Kane TSE (124 Canada), Thomas ZENG (124 Canada), Karey SHUMANSKY (124 Canada), Andrew J.L. ROTH (124 Canada), Sohrab SHAH (124 Canada), Hamza FAROOQ (124 Canada), Noriyuki KIJIMA (124 Canada), Borja L. HOLGADO (124 Canada), John J.Y. LEE (124 Canada), Stuart MATAN-LITHWICK (124 Canada), Jessica LIU (124 Canada), Stephen C. MACK (124 Canada), Alex MANNO (124 Canada), K.A. MICHEALRAJ (124 Canada), Carolina NOR (124 Canada), John PEACOCK (124 Canada), Lei QIN (124 Canada), Juri REIMAND (124 Canada), Adi ROLIDER (124 Canada), Yuan Y. THOMPSON (124 Canada), Xiaochong WU (124 Canada), Trevor PUGH (124 Canada), Adrian ALLY (124 Canada), Mikhail BILENKY (124 Canada), Yaron S.N. BUTTERFIELD (124 Canada), Rebecca CARLSEN (124 Canada), Young CHENG (124 Canada), Eric CHUAH (124 Canada), Richard D. CORBETT (124 Canada), Noreen DHALLA (124 Canada), An HE (124 Canada), Darlene LEE (124 Canada), Haiyan I. LI (124 Canada), William LONG (124 Canada), Michael MAYO (124 Canada), Patrick PLETTNER (124 Canada), Jenny Q. QIAN (124 Canada), Jacqueline E. SCHEIN (124 Canada), Angela TAM (124 Canada), Tina WONG (124 Canada), Inanc BIROL (124 Canada), Yongjun ZHAO (124 Canada), Claudia C. FARIA (620 Portugal), José PIMENTEL (620 Portugal), Sofia NUNES (620 Portugal), Tarek SHALABY (756 Switzerland), Michael GROTZER (756 Switzerland), Ian F. POLLACK (840 United States of America), Ronald L. HAMILTON (840 United States of America), Xiao-Nan LI (840 United States of America), Anne E. BENDEL (840 United States of America), Daniel W. FULTS (840 United States of America), Andrew W. WALTER (840 United States of America), Toshihiro KUMABE (392 Japan), Teiji TOMINAGA (392 Japan), V. Peter COLLINS (826 United Kingdom of Great Britain and Northern Ireland), Yoon-Jae CHO (840 United States of America), Caitlin HOFFMAN (124 Canada), David LYDEN (840 United States of America), Jeffrey H. WISOFF (840 United States of America), James H. GARVIN JR (840 United States of America), Duncan S. STEARNS (840 United States of America), Luca MASSIMI (380 Italy), Ulrich SCHÜLLER (276 Germany), Jaroslav ŠTĚRBA (203 Czech Republic, belonging to the institution), Karel ZITTERBART (203 Czech Republic, guarantor, belonging to the institution), Stephanie PUGET (250 France), Olivier AYRAULT (250 France), Sandra E. DUNN (124 Canada), Daniela P.C. TIRAPELLI (76 Brazil), Carlos G. CARLOTTI (76 Brazil), Helen WHEELER (36 Australia), Andrew R. HALLAHAN (36 Australia), Wendy INGRAM (36 Australia), Tobey J. MACDONALD (840 United States of America), Jeffrey J. OLSON (840 United States of America), Erwin G. Van MEIR (840 United States of America), Ji-Yeoun LEE (410 Republic of Korea), Kyu-Chang WANG (410 Republic of Korea), Seung-Ki KIM (410 Republic of Korea), Byung-Kyu CHO (410 Republic of Korea), Torsten PIETSCH (276 Germany), Gudrun FLEISCHHACK (276 Germany), Stephan TIPPELT (276 Germany), Young Shin RA (410 Republic of Korea), Simon BAILEY (826 United Kingdom of Great Britain and Northern Ireland), Janet C. LINDSEY (705 Slovenia), Steven C. CLIFFORD (826 United Kingdom of Great Britain and Northern Ireland), Charles G. EBERHART (840 United States of America), Michael K. COOPER (840 United States of America), Roger J. PACKER (840 United States of America), Maura MASSIMINO (380 Italy), Maria Luisa GARRE (380 Italy), Ute BARTELS (124 Canada), Uri TABORI (124 Canada), Cynthia E. HAWKINS (124 Canada), Peter DIRKS (124 Canada), Eric BOUFFET (124 Canada), James T. RUTKA (124 Canada), Robert J. WECHSLER-REYA (840 United States of America), William A. WEISS (840 United States of America), Lara S. COLLIER (840 United States of America), Adam J. DUPUY (840 United States of America), Andrey KORSHUNOV (276 Germany), David T.W. JONES (276 Germany), Marcel KOOL (276 Germany), Paul A. NORTHCOTT (276 Germany), Stefan M. PFISTER (276 Germany), David A. LARGAESPADA (840 United States of America), Andrew J. MUNGALL (124 Canada), Richard A. MOORE (124 Canada), Nada JABADO (124 Canada), Gary D. BADER (124 Canada), Steven J.M. JONES (124 Canada), David MALKIN (124 Canada), Marco A. MARRA (124 Canada) and Michael D. TAYLOR (124 Canada)

Edition

Nature, London, Nature Publishing Group, 2016, 0028-0836

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 40.137

RIV identification code

RIV/00216224:14110/16:00092045

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/nature16478

UT WoS

000368354800037

Keywords in English

SUBGROUP MEDULLOBLASTOMA; LYMPHOBLASTIC-LEUKEMIA; CANCER EVOLUTION; SEQUENCING DATA; GENOME; MUTATIONS; HETEROGENEITY; DYNAMICS; IMPACT; CELLS

Abstract

V originále

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.

Citovat

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 and Michael D. TAYLOR. Divergent clonal selection dominates medulloblastoma at recurrence. Nature. London: Nature Publishing Group, 2016, vol. 529, No 7586, p. 351-371. ISSN 0028-0836. Available from: https://dx.doi.org/10.1038/nature16478.

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   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 = {http://dx.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 and Michael D. TAYLOR. Divergent clonal selection dominates medulloblastoma at recurrence. \textit{Nature}. London: Nature Publishing Group, 2016, vol.~529, No~7586, p.~351-371. ISSN~0028-0836. Available from: https://dx.doi.org/10.1038/nature16478.

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