Medulloblastoma Comprises Four Distinct Molecular Variants

Northcott, Paul A.; Korshunov, Andrey; Witt, Hendrik; Hielscher, Thomas; Eberhart, Charles G.; Mack, Stephen C.; Bouffet, Éric; Clifford, Steven C.; Hawkins, Cynthia; French, Pim J.; Rutka, James T.; Pfister, Stefan M.; Taylor, Michael D.

doi:10.1200/jco.2009.27.4324

Cited by 1,136 publications

(1,427 citation statements)

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“…The main limitation of this study is the lack of information on molecular status of the tumours. Although distinct subgroups of medulloblastoma and CNS PNET have been established (7)(8)(9)(10)(11)(12)(13), these subgroups are not as yet classified as separate entities according to WHO or the ICCC-3.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, molecular testing of CNS tumours has evolved. Medulloblastomas are considered to comprise at least four distinct diseases that differ according to their demographic characteristics, histology, genetics and clinical outcomes (7)(8)(9). The CNS PNET subgroup refers to a heterogeneous group of tumours that show aggressive clinical behaviour.…”

Section: Introductionmentioning

confidence: 99%

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Incidence and survival of children and young people with central nervous system embryonal tumours in the North of England, 1990–2013

Fairley

Picton

McNally

et al. 2016

European Journal of Cancer

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Incidence and survival of children and young people with central nervous system embryonal tumours in the North of England, 1990–2013

Fairley

Picton

McNally

et al. 2016

European Journal of Cancer

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“…Interestingly, the group of patients with the longest PSIs had lower stage disease at diagnosis and a better overall survival probability than that with shorter PSIs [6]. The likely explanation for these results probably lies in the broad spectrum of biologic behaviour within the whole group of MB [3,15]. The present tumour can be classified histologically as WNT pathway-activated MB.…”

Section: Discussionmentioning

confidence: 63%

“…The present tumour can be classified histologically as WNT pathway-activated MB. This MB subtype is associated with a favourable prognosis [5,15]. One could speculate that the tumour acquired a stepwise accumulation of genetic aberrations over time, which -after a relatively stable phase -resulted in accelerated growth.…”

Section: Discussionmentioning

confidence: 99%

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Natural history of a medulloblastoma: 30 months of wait and see in a child with a cerebellar incidentaloma

et al. 2013

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INTRODUCTION:With the increasing use of neuroimaging studies, the discovery of incidental neoplastic lesions is becoming more frequent. However, standard procedures are lacking, and little is known about their optimal management. CASE REPORT: We here present the case of a boy with a cerebellar mass incidentally discovered on a CT scan performed after head trauma. In another scan performed after another incident of head trauma 14 months earlier, the lesion could be seen after retrospective examination. In view of the asymptomatic clinical and stable radiological status and the presumed diagnosis of a low-grade glioma, a watch-and-wait strategy was elected. After clinical and radiological progression was observed, the tumour was resected, 2½ years after the initial imaging study. Histological evaluation revealed a WNT pathway-activated classical medulloblastoma. DISCUSSION: To our knowledge, this is the first description of such a long natural history and pre-symptomatic period of a medulloblastoma. The long period of stability followed by a period of accelerated tumour growth is compatible with increasing biological aggressiveness, possibly related to the stepwise accumulation of genetic changes. DOI: https://doi.org/10.1007/s00381-013-2077-9Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-81611 Accepted Version Originally published at: Zeilhofer, Ulrike B; Scheer, Ianina; Warmuth-Metz, Monika; Rushing, Elisabeth J; Pietsch, Torsten; Boltshauser, Eugen; Grotzer, Michael A; Gerber, Nicolas U (2013). Natural history of a medulloblastoma: 30 months of wait and see in a child with a cerebellar incidentaloma. Child's Nervous System, 29 (7) ABSTRACTWith the increasing use of neuroimaging studies, the discovery of incidental neoplastic lesions is becoming more frequent. However, standard procedures are lacking and little is known about their optimal management. We here present the case of a boy with a cerebellar mass incidentally discovered on a CT scan performed after head trauma. In another scan performed after another incident of head trauma 4 months earlier, the lesion could be seen after retrospective examination. In view of the asymptomatic clinical and stable radiological status and the presumed diagnosis of a low-grade glioma, a watch-and-wait strategy was elected. After clinical and radiological progression was observed, the tumour was resected, 2½ years after the initial imaging study. Histological evaluation revealed a WNT pathway-activated classical medulloblastoma. To our knowledge, this is the first description of such a long natural history and pre-symptomatic period of a medulloblastoma. The long period of stability followed by a period of accelerated tumour growth is compatible with increasing biological aggressiveness, possibly related to the stepwise accumulation of genetic changes.

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Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth

Mody

Lonigro

et al. 2015

JAMA

346

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Importance Cancer is caused by a diverse array of somatic and germline genomic aberrations. Advances in genomic sequencing technologies have improved the ability to detect these molecular aberrations with greater sensitivity. However, integrating them into clinical management in an individualized manner has proven challenging. Objective To evaluate the use of integrative clinical sequencing and genetic counseling in the assessment and treatment of children and young adults with cancer. Design, Settings and Participants An observational, consecutive case series (May 2012–October 2014) of 102 children and young adults (mean age, 10.6; median age, 11.5, range: 0–22 years) with relapsed, refractory, or rare cancer at a single major academic medical center. Exposures Each participant underwent integrative clinical exome (tumor and germline DNA) and transcriptome (tumor RNA) sequencing along with genetic counseling. Results were discussed in a multi-disciplinary Precision Medicine Tumor Board (PMTB) and recommendations were reported to treating physicians and families. Main Outcomes and Measures Proportion of patients with potentially actionable findings (PAF), results of clinical actions based on integrative clinical sequencing (ICS), and estimated proportion of patients or their families at risk for future cancer. PAF was defined as any genomic findings discovered during sequencing analysis that could lead to a 1) change in patient management by providing a targetable molecular aberration, 2) change in diagnosis or risk stratification or 3) provides cancer-related germline findings, which inform patients/families about a potential future risk of various cancers; Results We screened 104 patients and enrolled 102 patients of which 91 (89%) had adequate tumor tissue available to complete sequencing and only these patients were included in all subsequent calculations, including 28 (31%) with hematological malignancies and 63 (69%) with solid tumors. Overall, 42 (46%) patients had PAFs which changed patient management including, 54% (15/28) with hematological malignancies and 43% (27/63) with solid tumors. Overall, individualized actions were taken in 23 of the 91 (25%) patients and families based on actionable ICS findings, including change in treatment in 14 (15%) and genetic counseling for future cancer risk in 9 (10%) patients. 9/91 (10%) of these personalized clinical interventions resulted in ongoing partial clinical remission of 8–16 months duration or help sustain complete clinical remission of 6–21 months duration. All 9 (10%) patients and families with actionable incidental genetic findings agreed to formal genetic counseling and screening. Conclusions and Relevance In this single center case series of children and young adults with relapsed or refractory cancer, incorporation of data from integrative clinical sequencing into clinical management was feasible, revealed potentially actionable findings in 46% of patients, and was associated with change in treatment and family genetic counseling in a s...

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Medulloblastoma Comprises Four Distinct Molecular Variants

Cited by 1,136 publications

References 33 publications

Incidence and survival of children and young people with central nervous system embryonal tumours in the North of England, 1990–2013

Incidence and survival of children and young people with central nervous system embryonal tumours in the North of England, 1990–2013

Natural history of a medulloblastoma: 30 months of wait and see in a child with a cerebellar incidentaloma

Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth

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