Subgroup-Specific Prognostic Implications of TP53 Mutation in Medulloblastoma

N Zhukova; V Ramaswamy; M Remke; E Pfaff; DJH Shih; DC Martin; P Castelo-Branco; B Baskin; PN Ray; E Bouffet; AO von Bueren; DTW Jones; PA Northcott; D Sturm; TJ Pugh; SL Pomeroy; YJ Cho; T Pietsch; M Gessi; S Rutkowski; L Bognar; A Klekner; BK Cho; SK Kim; KC Wang; CG Eberhart; M Fevre-Montange; M Fouladi; Pim French; J.M. Kros; WA Grajkowska; N Gupta; WA Weiss; P Hauser; N Jabado; A Jouvet; S Jung; T Kumabe; B Lach; JR Leonard; JB Rubin; LM Liau; L Massimi; IF Pollack; YS Ra; EG van Meir; K Zitterbart; U Schueller; RM Hill; JC Lindsey; EC Schwalbe; S Bailey; DW Ellison; C Hawkins; D Malkin; SC Clifford; A Korshunov; S Pfister; MD Taylor; U Tabori; Mirjam Kool

doi:10.1200/JCO.2012.48.5052

Subgroup-Specific Prognostic Implications of TP53 Mutation in Medulloblastoma

N Zhukova, V Ramaswamy, M Remke, E Pfaff, DJH Shih, DC Martin, P Castelo-Branco, B Baskin, PN Ray, E Bouffet, AO von Bueren, DTW Jones, PA Northcott, D Sturm, TJ Pugh, SL Pomeroy, YJ Cho, T Pietsch, M Gessi, S RutkowskiL Bognar, A Klekner, BK Cho, SK Kim, KC Wang, CG Eberhart, M Fevre-Montange, M Fouladi, Pim French, J.M. Kros, WA Grajkowska, N Gupta, WA Weiss, P Hauser, N Jabado, A Jouvet, S Jung, T Kumabe, B Lach, JR Leonard, JB Rubin, LM Liau, L Massimi, IF Pollack, YS Ra, EG van Meir, K Zitterbart, U Schueller, RM Hill, JC Lindsey, EC Schwalbe, S Bailey, DW Ellison, C Hawkins, D Malkin, SC Clifford, A Korshunov, S Pfister, MD Taylor, U Tabori, Mirjam Kool

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

390 Citations (Scopus)

Abstract

Purpose Reports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through the inclusion of molecular subgroup profiles. Patients and Methods We determined subgroup affiliation, TP53 mutation status, and clinical outcome in a discovery cohort of 397 medulloblastomas. We subsequently validated our results on an independent cohort of 156 medulloblastomas. Results TP53 mutations are enriched in wingless (WNT; 16%) and sonic hedgehog (SHH; 21%) medulloblastomas and are virtually absent in subgroups 3 and 4 tumors (P < .001). Patients with SHH/TP53 mutant tumors are almost exclusively between ages 5 and 18 years, dramatically different from the general SHH distribution (P < .001). Children with SHH/TP53 mutant tumors harbor 56% germline TP53 mutations, which are not observed in children with WNT/TP53 mutant tumors. Five-year overall survival (OS; +/- SE) wa Conclusion Subgroup-specific analysis reconciles prior conflicting publications and confirms that TP53 mutations are enriched among SHH medulloblastomas, in which they portend poor outcome and account for a large proportion of treatment failures in these patients. (C) 2013 by American Society of Clinical Oncology

Original language	English
Pages (from-to)	2927-+
Journal	Journal of Clinical Oncology
Volume	31
Issue number	23
DOIs	https://doi.org/10.1200/JCO.2012.48.5052
Publication status	Published - 2013

Research programs

EMC MM-03-44-06

Access to Document

10.1200/JCO.2012.48.5052

Cite this

Zhukova, N., Ramaswamy, V., Remke, M., Pfaff, E., Shih, DJH., Martin, DC., Castelo-Branco, P., Baskin, B., Ray, PN., Bouffet, E., von Bueren, AO., Jones, DTW., Northcott, PA., Sturm, D., Pugh, TJ., Pomeroy, SL., Cho, YJ., Pietsch, T., Gessi, M., ... Kool, M. (2013). Subgroup-Specific Prognostic Implications of TP53 Mutation in Medulloblastoma. Journal of Clinical Oncology, 31(23), 2927-+. https://doi.org/10.1200/JCO.2012.48.5052

@article{1e727c33d32741e684db373c9a1b6a75,

title = "Subgroup-Specific Prognostic Implications of TP53 Mutation in Medulloblastoma",

abstract = "Purpose Reports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through the inclusion of molecular subgroup profiles. Patients and Methods We determined subgroup affiliation, TP53 mutation status, and clinical outcome in a discovery cohort of 397 medulloblastomas. We subsequently validated our results on an independent cohort of 156 medulloblastomas. Results TP53 mutations are enriched in wingless (WNT; 16%) and sonic hedgehog (SHH; 21%) medulloblastomas and are virtually absent in subgroups 3 and 4 tumors (P < .001). Patients with SHH/TP53 mutant tumors are almost exclusively between ages 5 and 18 years, dramatically different from the general SHH distribution (P < .001). Children with SHH/TP53 mutant tumors harbor 56% germline TP53 mutations, which are not observed in children with WNT/TP53 mutant tumors. Five-year overall survival (OS; +/- SE) wa Conclusion Subgroup-specific analysis reconciles prior conflicting publications and confirms that TP53 mutations are enriched among SHH medulloblastomas, in which they portend poor outcome and account for a large proportion of treatment failures in these patients. (C) 2013 by American Society of Clinical Oncology",

author = "N Zhukova and V Ramaswamy and M Remke and E Pfaff and DJH Shih and DC Martin and P Castelo-Branco and B Baskin and PN Ray and E Bouffet and {von Bueren}, AO and DTW Jones and PA Northcott and D Sturm and TJ Pugh and SL Pomeroy and YJ Cho and T Pietsch and M Gessi and S Rutkowski and L Bognar and A Klekner and BK Cho and SK Kim and KC Wang and CG Eberhart and M Fevre-Montange and M Fouladi and Pim French and J.M. Kros and WA Grajkowska and N Gupta and WA Weiss and P Hauser and N Jabado and A Jouvet and S Jung and T Kumabe and B Lach and JR Leonard and JB Rubin and LM Liau and L Massimi and IF Pollack and YS Ra and {van Meir}, EG and K Zitterbart and U Schueller and RM Hill and JC Lindsey and EC Schwalbe and S Bailey and DW Ellison and C Hawkins and D Malkin and SC Clifford and A Korshunov and S Pfister and MD Taylor and U Tabori and Mirjam Kool",

year = "2013",

doi = "10.1200/JCO.2012.48.5052",

language = "English",

volume = "31",

pages = "2927--+",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "Lippincott Williams & Wilkins",

number = "23",

}

Zhukova, N, Ramaswamy, V, Remke, M, Pfaff, E, Shih, DJH, Martin, DC, Castelo-Branco, P, Baskin, B, Ray, PN, Bouffet, E, von Bueren, AO, Jones, DTW, Northcott, PA, Sturm, D, Pugh, TJ, Pomeroy, SL, Cho, YJ, Pietsch, T, Gessi, M, Rutkowski, S, Bognar, L, Klekner, A, Cho, BK, Kim, SK, Wang, KC, Eberhart, CG, Fevre-Montange, M, Fouladi, M, French, P, Kros, JM, Grajkowska, WA, Gupta, N, Weiss, WA, Hauser, P, Jabado, N, Jouvet, A, Jung, S, Kumabe, T, Lach, B, Leonard, JR, Rubin, JB, Liau, LM, Massimi, L, Pollack, IF, Ra, YS, van Meir, EG, Zitterbart, K, Schueller, U, Hill, RM, Lindsey, JC, Schwalbe, EC, Bailey, S, Ellison, DW, Hawkins, C, Malkin, D, Clifford, SC, Korshunov, A, Pfister, S, Taylor, MD, Tabori, U & Kool, M 2013, 'Subgroup-Specific Prognostic Implications of TP53 Mutation in Medulloblastoma', Journal of Clinical Oncology, vol. 31, no. 23, pp. 2927-+. https://doi.org/10.1200/JCO.2012.48.5052

TY - JOUR

T1 - Subgroup-Specific Prognostic Implications of TP53 Mutation in Medulloblastoma

AU - Zhukova, N

AU - Ramaswamy, V

AU - Remke, M

AU - Pfaff, E

AU - Shih, DJH

AU - Martin, DC

AU - Castelo-Branco, P

AU - Baskin, B

AU - Ray, PN

AU - Bouffet, E

AU - von Bueren, AO

AU - Jones, DTW

AU - Northcott, PA

AU - Sturm, D

AU - Pugh, TJ

AU - Pomeroy, SL

AU - Cho, YJ

AU - Pietsch, T

AU - Gessi, M

AU - Rutkowski, S

AU - Bognar, L

AU - Klekner, A

AU - Cho, BK

AU - Kim, SK

AU - Wang, KC

AU - Eberhart, CG

AU - Fevre-Montange, M

AU - Fouladi, M

AU - French, Pim

AU - Kros, J.M.

AU - Grajkowska, WA

AU - Gupta, N

AU - Weiss, WA

AU - Hauser, P

AU - Jabado, N

AU - Jouvet, A

AU - Jung, S

AU - Kumabe, T

AU - Lach, B

AU - Leonard, JR

AU - Rubin, JB

AU - Liau, LM

AU - Massimi, L

AU - Pollack, IF

AU - Ra, YS

AU - van Meir, EG

AU - Zitterbart, K

AU - Schueller, U

AU - Hill, RM

AU - Lindsey, JC

AU - Schwalbe, EC

AU - Bailey, S

AU - Ellison, DW

AU - Hawkins, C

AU - Malkin, D

AU - Clifford, SC

AU - Korshunov, A

AU - Pfister, S

AU - Taylor, MD

AU - Tabori, U

AU - Kool, Mirjam

PY - 2013

Y1 - 2013

N2 - Purpose Reports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through the inclusion of molecular subgroup profiles. Patients and Methods We determined subgroup affiliation, TP53 mutation status, and clinical outcome in a discovery cohort of 397 medulloblastomas. We subsequently validated our results on an independent cohort of 156 medulloblastomas. Results TP53 mutations are enriched in wingless (WNT; 16%) and sonic hedgehog (SHH; 21%) medulloblastomas and are virtually absent in subgroups 3 and 4 tumors (P < .001). Patients with SHH/TP53 mutant tumors are almost exclusively between ages 5 and 18 years, dramatically different from the general SHH distribution (P < .001). Children with SHH/TP53 mutant tumors harbor 56% germline TP53 mutations, which are not observed in children with WNT/TP53 mutant tumors. Five-year overall survival (OS; +/- SE) wa Conclusion Subgroup-specific analysis reconciles prior conflicting publications and confirms that TP53 mutations are enriched among SHH medulloblastomas, in which they portend poor outcome and account for a large proportion of treatment failures in these patients. (C) 2013 by American Society of Clinical Oncology

AB - Purpose Reports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through the inclusion of molecular subgroup profiles. Patients and Methods We determined subgroup affiliation, TP53 mutation status, and clinical outcome in a discovery cohort of 397 medulloblastomas. We subsequently validated our results on an independent cohort of 156 medulloblastomas. Results TP53 mutations are enriched in wingless (WNT; 16%) and sonic hedgehog (SHH; 21%) medulloblastomas and are virtually absent in subgroups 3 and 4 tumors (P < .001). Patients with SHH/TP53 mutant tumors are almost exclusively between ages 5 and 18 years, dramatically different from the general SHH distribution (P < .001). Children with SHH/TP53 mutant tumors harbor 56% germline TP53 mutations, which are not observed in children with WNT/TP53 mutant tumors. Five-year overall survival (OS; +/- SE) wa Conclusion Subgroup-specific analysis reconciles prior conflicting publications and confirms that TP53 mutations are enriched among SHH medulloblastomas, in which they portend poor outcome and account for a large proportion of treatment failures in these patients. (C) 2013 by American Society of Clinical Oncology

UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878050/

U2 - 10.1200/JCO.2012.48.5052

DO - 10.1200/JCO.2012.48.5052

M3 - Article

C2 - 23835706

SN - 0732-183X

VL - 31

SP - 2927-+

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 23

ER -

Subgroup-Specific Prognostic Implications of TP53 Mutation in Medulloblastoma

Abstract

Research programs

Access to Document

Other files and links

Fingerprint

Cite this