guest ::
| Home > Publications database > Molecular and clinical heterogeneity within MYC-family amplified medulloblastoma is associated with survival outcomes: A multicenter cohort study. > print |
| Home > Publications database > Molecular and clinical heterogeneity within MYC-family amplified medulloblastoma is associated with survival outcomes: A multicenter cohort study. > print |
| 001 | 293955 | ||
| 005 | 20250113142956.0 | ||
| 024 | 7 | _ | |a 10.1093/neuonc/noae178 |2 doi |
| 024 | 7 | _ | |a pmid:39377358 |2 pmid |
| 024 | 7 | _ | |a 1522-8517 |2 ISSN |
| 024 | 7 | _ | |a 1523-5866 |2 ISSN |
| 024 | 7 | _ | |a altmetric:169088976 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2024-02020 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Schwalbe, Edward C |b 0 |
| 245 | _ | _ | |a Molecular and clinical heterogeneity within MYC-family amplified medulloblastoma is associated with survival outcomes: A multicenter cohort study. |
| 260 | _ | _ | |a Oxford |c 2025 |b Oxford Univ. Press |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1736774946_3204 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a Volume 27, Issue 1, January 2025, Pages 222–236 |
| 520 | _ | _ | |a MYC/MYCN are the most frequent oncogene amplifications in medulloblastoma (MB) and its primary biomarkers of high-risk (HR) disease. However, while many patients' MYC(N)-amplified tumors are treatment-refractory, some achieve long-term survival. We therefore investigated clinicobiological heterogeneity within MYC(N)-amplified MB and determined its relevance for improved disease management.We characterized the clinical and molecular correlates of MYC- (MYC-MB; n = 64) and MYCN-amplified MBs (MYCN-MB; n = 95), drawn from >1600 diagnostic cases.Most MYC-MBs were molecular group 3 (46/58; 79% assessable) and aged ≥3 years at diagnosis (44/64 [69%]). We identified a 'canonical' very high-risk (VHR) MYC-amplified group (n = 51/62; 82%) with dismal survival irrespective of treatment (11% 5-year progression-free survival [PFS]), defined by co-occurrence with ≥1 additional established risk factor(s) (subtotal surgical-resection [STR], metastatic disease, LCA pathology), and commonly group 3/4 subgroup 2 with a high proportion of amplified cells. The majority of remaining noncanonical MYC-MBs survived (i.e. non-group 3/group 3 without other risk features; 11/62 (18%); 61% 5-year PFS). MYCN survival was primarily related to molecular group; MYCN-amplified SHH MB, and group 3/4 MB with additional risk factors, respectively defined VHR and HR groups (VHR, 39% [35/89]; 20% 5-year PFS/HR, 33% [29/89]; 46% 5-year PFS). Twenty-two out of 35 assessable MYCN-amplified SHH tumors harbored TP53 mutations; 9/12 (75%) with data were germline. MYCN-amplified group 3/4 MB with no other risk factors (28%; 25/89) had 70% 5-year PFS.MYC(N)-amplified MB displays significant clinicobiological heterogeneity. Diagnostics incorporating molecular groups, subgroups, and clinical factors enable their risk assessment. VHR 'canonical' MYC tumors are essentially incurable and SHH-MYCN-amplified MBs fare extremely poorly (20% survival at 5 years); both require urgent development of alternative treatment strategies. Conventional risk-adapted therapies are appropriate for more responsive groups, such as noncanonical MYC and non-SHH-MYCN MB. |
| 536 | _ | _ | |a 312 - Funktionelle und strukturelle Genomforschung (POF4-312) |0 G:(DE-HGF)POF4-312 |c POF4-312 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de |
| 650 | _ | 7 | |a MYC amplification |2 Other |
| 650 | _ | 7 | |a MYCN amplification |2 Other |
| 650 | _ | 7 | |a medulloblastoma |2 Other |
| 650 | _ | 7 | |a survival |2 Other |
| 700 | 1 | _ | |a Lindsey, Janet C |b 1 |
| 700 | 1 | _ | |a Danilenko, Marina |b 2 |
| 700 | 1 | _ | |a Hill, Rebecca M |b 3 |
| 700 | 1 | _ | |a Crosier, Stephen |b 4 |
| 700 | 1 | _ | |a Ryan, Sarra L |b 5 |
| 700 | 1 | _ | |a Williamson, Daniel |b 6 |
| 700 | 1 | _ | |a Castle, Jemma |b 7 |
| 700 | 1 | _ | |a Hicks, Debbie |b 8 |
| 700 | 1 | _ | |a Kool, Marcel |0 P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8 |b 9 |
| 700 | 1 | _ | |a Milde, Till |0 P:(DE-He78)0be2f86573954f87e97f8a4dbb05cb0f |b 10 |u dkfz |
| 700 | 1 | _ | |a Korshunov, Andrey |0 P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93 |b 11 |u dkfz |
| 700 | 1 | _ | |a Pfister, Stefan M |0 P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9 |b 12 |u dkfz |
| 700 | 1 | _ | |a Bailey, Simon |b 13 |
| 700 | 1 | _ | |a Clifford, Steven C |0 0000-0003-4893-2184 |b 14 |
| 773 | _ | _ | |a 10.1093/neuonc/noae178 |g p. noae178 |0 PERI:(DE-600)2094060-9 |n 1 |p 222–236 |t Neuro-Oncology |v 27 |y 2025 |x 1522-8517 |
| 909 | C | O | |p VDB |o oai:inrepo02.dkfz.de:293955 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 9 |6 P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 10 |6 P:(DE-He78)0be2f86573954f87e97f8a4dbb05cb0f |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 11 |6 P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 12 |6 P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9 |
| 913 | 1 | _ | |a DE-HGF |b Gesundheit |l Krebsforschung |1 G:(DE-HGF)POF4-310 |0 G:(DE-HGF)POF4-312 |3 G:(DE-HGF)POF4 |2 G:(DE-HGF)POF4-300 |4 G:(DE-HGF)POF |v Funktionelle und strukturelle Genomforschung |x 0 |
| 914 | 1 | _ | |y 2024 |
| 915 | _ | _ | |a Nationallizenz |0 StatID:(DE-HGF)0420 |2 StatID |d 2023-10-24 |w ger |
| 915 | _ | _ | |a JCR |0 StatID:(DE-HGF)0100 |2 StatID |b NEURO-ONCOLOGY : 2022 |d 2023-10-24 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |d 2023-10-24 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |d 2023-10-24 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0320 |2 StatID |b PubMed Central |d 2023-10-24 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |d 2023-10-24 |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0113 |2 StatID |b Science Citation Index Expanded |d 2023-10-24 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |d 2023-10-24 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0160 |2 StatID |b Essential Science Indicators |d 2023-10-24 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1110 |2 StatID |b Current Contents - Clinical Medicine |d 2023-10-24 |
| 915 | _ | _ | |a IF >= 15 |0 StatID:(DE-HGF)9915 |2 StatID |b NEURO-ONCOLOGY : 2022 |d 2023-10-24 |
| 920 | 1 | _ | |0 I:(DE-He78)B062-20160331 |k B062 |l B062 Pädiatrische Neuroonkologie |x 0 |
| 920 | 1 | _ | |0 I:(DE-He78)HD01-20160331 |k HD01 |l DKTK HD zentral |x 1 |
| 920 | 1 | _ | |0 I:(DE-He78)B300-20160331 |k B300 |l KKE Neuropathologie |x 2 |
| 920 | 1 | _ | |0 I:(DE-He78)B310-20160331 |k B310 |l KKE Pädiatrische Onkologie |x 3 |
| 980 | _ | _ | |a journal |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a I:(DE-He78)B062-20160331 |
| 980 | _ | _ | |a I:(DE-He78)HD01-20160331 |
| 980 | _ | _ | |a I:(DE-He78)B300-20160331 |
| 980 | _ | _ | |a I:(DE-He78)B310-20160331 |
| 980 | _ | _ | |a UNRESTRICTED |
| Library | Collection | CLSMajor | CLSMinor | Language | Author |
|---|