Intertumoral Heterogeneity within Medulloblastoma Subgroups

Florence M.G. Cavalli; Marc Remke; Ladislav Rampasek; John Peacock; David J.H. Shih; Betty Luu; Livia Garzia; Jonathon Torchia; Carolina Nor; A. Sorana Morrissy; Sameer Agnihotri; Yuan Yao Thompson; Claudia M. Kuzan-Fischer; Hamza Farooq; Keren Isaev; Craig Daniels; Byung Kyu Cho; Seung Ki Kim; Kyu Chang Wang; Ji Yeoun Lee; Wieslawa A. Grajkowska; Marta Perek-Polnik; Alexandre Vasiljevic; Cecile Faure-Conter; Anne Jouvet; Caterina Giannini; Amulya A. Nageswara Rao; Kay Ka Wai Li; Ho Keung Ng; Charles G. Eberhart; Ian F. Pollack; Ronald L. Hamilton; G. Yancey Gillespie; James M. Olson; Sarah Leary; William A. Weiss; Boleslaw Lach; Lola B. Chambless; Reid C. Thompson; Michael K. Cooper; Rajeev Vibhakar; Peter Hauser; Marie Lise C. van Veelen; Johan M. Kros; Pim J. French; Young Shin Ra; Toshihiro Kumabe; Enrique López-Aguilar; Karel Zitterbart; Jaroslav Sterba; Gaetano Finocchiaro; Maura Massimino; Erwin G. Van Meir; Satoru Osuka; Tomoko Shofuda; Almos Klekner; Massimo Zollo; Jeffrey R. Leonard; Joshua B. Rubin; Nada Jabado; Steffen Albrecht; Jaume Mora; Timothy E. Van Meter; Shin Jung; Andrew S. Moore; Andrew R. Hallahan; Jennifer A. Chan; Daniela P.C. Tirapelli; Carlos G. Carlotti; Maryam Fouladi; José Pimentel; Claudia C. Faria; Ali G. Saad; Luca Massimi; Linda M. Liau; Helen Wheeler; Hideo Nakamura; Samer K. Elbabaa; Mario Perezpeña-Diazconti; Fernando Chico Ponce de León; Shenandoah Robinson; Michal Zapotocky; Alvaro Lassaletta; Annie Huang; Cynthia E. Hawkins; Uri Tabori; Eric Bouffet; Ute Bartels; Peter B. Dirks; James T. Rutka; Gary D. Bader; Jüri Reimand; Anna Goldenberg; Vijay Ramaswamy; Michael D. Taylor

doi:10.1016/j.ccell.2017.05.005

Intertumoral Heterogeneity within Medulloblastoma Subgroups

Florence M.G. Cavalli, Marc Remke, Ladislav Rampasek, John Peacock, David J.H. Shih, Betty Luu, Livia Garzia, Jonathon Torchia, Carolina Nor, A. Sorana Morrissy, Sameer Agnihotri, Yuan Yao Thompson, Claudia M. Kuzan-Fischer, Hamza Farooq, Keren Isaev, Craig Daniels, Byung Kyu Cho, Seung Ki Kim, Kyu Chang Wang, Ji Yeoun LeeWieslawa A. Grajkowska, Marta Perek-Polnik, Alexandre Vasiljevic, Cecile Faure-Conter, Anne Jouvet, Caterina Giannini, Amulya A. Nageswara Rao, Kay Ka Wai Li, Ho Keung Ng, Charles G. Eberhart, Ian F. Pollack, Ronald L. Hamilton, G. Yancey Gillespie, James M. Olson, Sarah Leary, William A. Weiss, Boleslaw Lach, Lola B. Chambless, Reid C. Thompson, Michael K. Cooper, Rajeev Vibhakar, Peter Hauser, Marie Lise C. van Veelen, Johan M. Kros, Pim J. French, Young Shin Ra, Toshihiro Kumabe, Enrique López-Aguilar, Karel Zitterbart, Jaroslav Sterba, Gaetano Finocchiaro, Maura Massimino, Erwin G. Van Meir, Satoru Osuka, Tomoko Shofuda, Almos Klekner, Massimo Zollo, Jeffrey R. Leonard, Joshua B. Rubin, Nada Jabado, Steffen Albrecht, Jaume Mora, Timothy E. Van Meter, Shin Jung, Andrew S. Moore, Andrew R. Hallahan, Jennifer A. Chan, Daniela P.C. Tirapelli, Carlos G. Carlotti, Maryam Fouladi, José Pimentel, Claudia C. Faria, Ali G. Saad, Luca Massimi, Linda M. Liau, Helen Wheeler, Hideo Nakamura, Samer K. Elbabaa, Mario Perezpeña-Diazconti, Fernando Chico Ponce de León, Shenandoah Robinson, Michal Zapotocky, Alvaro Lassaletta, Annie Huang, Cynthia E. Hawkins, Uri Tabori, Eric Bouffet, Ute Bartels, Peter B. Dirks, James T. Rutka, Gary D. Bader, Jüri Reimand, Anna Goldenberg, Vijay Ramaswamy, Michael D. Taylor

School of Medicine

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

360 Scopus citations

Abstract

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

Original language	English (US)
Pages (from-to)	737-754.e6
Journal	Cancer cell
Volume	31
Issue number	6
DOIs	https://doi.org/10.1016/j.ccell.2017.05.005
State	Published - Jun 12 2017

Keywords

copy number
gene expression
integrative clustering
medulloblastoma
methylation
subgroups

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccell.2017.05.005

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Cavalli, F. M. G., Remke, M., Rampasek, L., Peacock, J., Shih, D. J. H., Luu, B., Garzia, L., Torchia, J., Nor, C., Morrissy, A. S., Agnihotri, S., Thompson, Y. Y., Kuzan-Fischer, C. M., Farooq, H., Isaev, K., Daniels, C., Cho, B. K., Kim, S. K., Wang, K. C., ... Taylor, M. D. (2017). Intertumoral Heterogeneity within Medulloblastoma Subgroups. Cancer cell, 31(6), 737-754.e6. https://doi.org/10.1016/j.ccell.2017.05.005

Cavalli, FMG, Remke, M, Rampasek, L, Peacock, J, Shih, DJH, Luu, B, Garzia, L, Torchia, J, Nor, C, Morrissy, AS, Agnihotri, S, Thompson, YY, Kuzan-Fischer, CM, Farooq, H, Isaev, K, Daniels, C, Cho, BK, Kim, SK, Wang, KC, Lee, JY, Grajkowska, WA, Perek-Polnik, M, Vasiljevic, A, Faure-Conter, C, Jouvet, A, Giannini, C, Nageswara Rao, AA, Li, KKW, Ng, HK, Eberhart, CG, Pollack, IF, Hamilton, RL, Gillespie, GY, Olson, JM, Leary, S, Weiss, WA, Lach, B, Chambless, LB, Thompson, RC, Cooper, MK, Vibhakar, R, Hauser, P, van Veelen, MLC, Kros, JM, French, PJ, Ra, YS, Kumabe, T, López-Aguilar, E, Zitterbart, K, Sterba, J, Finocchiaro, G, Massimino, M, Van Meir, EG, Osuka, S, Shofuda, T, Klekner, A, Zollo, M, Leonard, JR, Rubin, JB, Jabado, N, Albrecht, S, Mora, J, Van Meter, TE, Jung, S, Moore, AS, Hallahan, AR, Chan, JA, Tirapelli, DPC, Carlotti, CG, Fouladi, M, Pimentel, J, Faria, CC, Saad, AG, Massimi, L, Liau, LM, Wheeler, H, Nakamura, H, Elbabaa, SK, Perezpeña-Diazconti, M, Chico Ponce de León, F, Robinson, S, Zapotocky, M, Lassaletta, A, Huang, A, Hawkins, CE, Tabori, U, Bouffet, E, Bartels, U, Dirks, PB, Rutka, JT, Bader, GD, Reimand, J, Goldenberg, A, Ramaswamy, V & Taylor, MD 2017, 'Intertumoral Heterogeneity within Medulloblastoma Subgroups', Cancer cell, vol. 31, no. 6, pp. 737-754.e6. https://doi.org/10.1016/j.ccell.2017.05.005

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title = "Intertumoral Heterogeneity within Medulloblastoma Subgroups",

abstract = "While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.",

keywords = "copy number, gene expression, integrative clustering, medulloblastoma, methylation, subgroups",

author = "Cavalli, {Florence M.G.} and Marc Remke and Ladislav Rampasek and John Peacock and Shih, {David J.H.} and Betty Luu and Livia Garzia and Jonathon Torchia and Carolina Nor and Morrissy, {A. Sorana} and Sameer Agnihotri and Thompson, {Yuan Yao} and Kuzan-Fischer, {Claudia M.} and Hamza Farooq and Keren Isaev and Craig Daniels and Cho, {Byung Kyu} and Kim, {Seung Ki} and Wang, {Kyu Chang} and Lee, {Ji Yeoun} and Grajkowska, {Wieslawa A.} and Marta Perek-Polnik and Alexandre Vasiljevic and Cecile Faure-Conter and Anne Jouvet and Caterina Giannini and {Nageswara Rao}, {Amulya A.} and Li, {Kay Ka Wai} and Ng, {Ho Keung} and Eberhart, {Charles G.} and Pollack, {Ian F.} and Hamilton, {Ronald L.} and Gillespie, {G. Yancey} and Olson, {James M.} and Sarah Leary and Weiss, {William A.} and Boleslaw Lach and Chambless, {Lola B.} and Thompson, {Reid C.} and Cooper, {Michael K.} and Rajeev Vibhakar and Peter Hauser and {van Veelen}, {Marie Lise C.} and Kros, {Johan M.} and French, {Pim J.} and Ra, {Young Shin} and Toshihiro Kumabe and Enrique L{\'o}pez-Aguilar and Karel Zitterbart and Jaroslav Sterba and Gaetano Finocchiaro and Maura Massimino and {Van Meir}, {Erwin G.} and Satoru Osuka and Tomoko Shofuda and Almos Klekner and Massimo Zollo and Leonard, {Jeffrey R.} and Rubin, {Joshua B.} and Nada Jabado and Steffen Albrecht and Jaume Mora and {Van Meter}, {Timothy E.} and Shin Jung and Moore, {Andrew S.} and Hallahan, {Andrew R.} and Chan, {Jennifer A.} and Tirapelli, {Daniela P.C.} and Carlotti, {Carlos G.} and Maryam Fouladi and Jos{\'e} Pimentel and Faria, {Claudia C.} and Saad, {Ali G.} and Luca Massimi and Liau, {Linda M.} and Helen Wheeler and Hideo Nakamura and Elbabaa, {Samer K.} and Mario Perezpe{\~n}a-Diazconti and {Chico Ponce de Le{\'o}n}, Fernando and Shenandoah Robinson and Michal Zapotocky and Alvaro Lassaletta and Annie Huang and Hawkins, {Cynthia E.} and Uri Tabori and Eric Bouffet and Ute Bartels and Dirks, {Peter B.} and Rutka, {James T.} and Bader, {Gary D.} and J{\"u}ri Reimand and Anna Goldenberg and Vijay Ramaswamy and Taylor, {Michael D.}",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = jun,

day = "12",

doi = "10.1016/j.ccell.2017.05.005",

language = "English (US)",

volume = "31",

pages = "737--754.e6",

journal = "Cancer cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Intertumoral Heterogeneity within Medulloblastoma Subgroups

AU - Cavalli, Florence M.G.

AU - Remke, Marc

AU - Rampasek, Ladislav

AU - Peacock, John

AU - Shih, David J.H.

AU - Luu, Betty

AU - Garzia, Livia

AU - Torchia, Jonathon

AU - Nor, Carolina

AU - Morrissy, A. Sorana

AU - Agnihotri, Sameer

AU - Thompson, Yuan Yao

AU - Kuzan-Fischer, Claudia M.

AU - Farooq, Hamza

AU - Isaev, Keren

AU - Daniels, Craig

AU - Cho, Byung Kyu

AU - Kim, Seung Ki

AU - Wang, Kyu Chang

AU - Lee, Ji Yeoun

AU - Grajkowska, Wieslawa A.

AU - Perek-Polnik, Marta

AU - Vasiljevic, Alexandre

AU - Faure-Conter, Cecile

AU - Jouvet, Anne

AU - Giannini, Caterina

AU - Nageswara Rao, Amulya A.

AU - Li, Kay Ka Wai

AU - Ng, Ho Keung

AU - Eberhart, Charles G.

AU - Pollack, Ian F.

AU - Hamilton, Ronald L.

AU - Gillespie, G. Yancey

AU - Olson, James M.

AU - Leary, Sarah

AU - Weiss, William A.

AU - Lach, Boleslaw

AU - Chambless, Lola B.

AU - Thompson, Reid C.

AU - Cooper, Michael K.

AU - Vibhakar, Rajeev

AU - Hauser, Peter

AU - van Veelen, Marie Lise C.

AU - Kros, Johan M.

AU - French, Pim J.

AU - Ra, Young Shin

AU - Kumabe, Toshihiro

AU - López-Aguilar, Enrique

AU - Zitterbart, Karel

AU - Sterba, Jaroslav

AU - Finocchiaro, Gaetano

AU - Massimino, Maura

AU - Van Meir, Erwin G.

AU - Osuka, Satoru

AU - Shofuda, Tomoko

AU - Klekner, Almos

AU - Zollo, Massimo

AU - Leonard, Jeffrey R.

AU - Rubin, Joshua B.

AU - Jabado, Nada

AU - Albrecht, Steffen

AU - Mora, Jaume

AU - Van Meter, Timothy E.

AU - Jung, Shin

AU - Moore, Andrew S.

AU - Hallahan, Andrew R.

AU - Chan, Jennifer A.

AU - Tirapelli, Daniela P.C.

AU - Carlotti, Carlos G.

AU - Fouladi, Maryam

AU - Pimentel, José

AU - Faria, Claudia C.

AU - Saad, Ali G.

AU - Massimi, Luca

AU - Liau, Linda M.

AU - Wheeler, Helen

AU - Nakamura, Hideo

AU - Elbabaa, Samer K.

AU - Perezpeña-Diazconti, Mario

AU - Chico Ponce de León, Fernando

AU - Robinson, Shenandoah

AU - Zapotocky, Michal

AU - Lassaletta, Alvaro

AU - Huang, Annie

AU - Hawkins, Cynthia E.

AU - Tabori, Uri

AU - Bouffet, Eric

AU - Bartels, Ute

AU - Dirks, Peter B.

AU - Rutka, James T.

AU - Bader, Gary D.

AU - Reimand, Jüri

AU - Goldenberg, Anna

AU - Ramaswamy, Vijay

AU - Taylor, Michael D.

PY - 2017/6/12

Y1 - 2017/6/12

N2 - While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

AB - While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

KW - copy number

KW - gene expression

KW - integrative clustering

KW - medulloblastoma

KW - methylation

KW - subgroups

UR - http://www.scopus.com/inward/record.url?scp=85020687117&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020687117&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2017.05.005

DO - 10.1016/j.ccell.2017.05.005

M3 - Article

C2 - 28609654

AN - SCOPUS:85020687117

SN - 1535-6108

VL - 31

SP - 737-754.e6

JO - Cancer cell

JF - Cancer cell

IS - 6

ER -

Intertumoral Heterogeneity within Medulloblastoma Subgroups

Abstract

Keywords

ASJC Scopus subject areas

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