Divergent clonal selection dominates medulloblastoma at recurrence

Morrissy, A. Sorana, Garzia, Livia, Shih, David J. H., 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, Jose, 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, James H., Jr., Stearns, Duncan S., Massimi, Luca, Schueller, Ulrich, Sterba, 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., Van Meir, Erwin G., 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. and Taylor, Michael D. (2016) Divergent clonal selection dominates medulloblastoma at recurrence. Nature, 529 7586: 351-357. doi:10.1038/nature16478


Author Morrissy, A. Sorana
Garzia, Livia
Shih, David J. H.
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, Jose
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, James H., Jr.
Stearns, Duncan S.
Massimi, Luca
Schueller, Ulrich
Sterba, 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.
Van Meir, Erwin G.
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.
Title Divergent clonal selection dominates medulloblastoma at recurrence
Journal name Nature   Check publisher's open access policy
ISSN 1476-4687
0028-0836
Publication date 2016-01-21
Year available 2016
Sub-type Article (original research)
DOI 10.1038/nature16478
Open Access Status Not yet assessed
Volume 529
Issue 7586
Start page 351
End page 357
Total pages 7
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Formatted abstract
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.
Keyword Anti-cancer therapies
Cancer genomes
Medulloblastoma
Divergent clonal selection
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Admin only - CHRC
Child Health Research Centre Publications
 
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