Subgroup-specific structural variation across 1,000 medulloblastoma genomes
By P. Northcott, D. Shih, J. Peacock, L. Garzia, A. Morrissy, T. Zichner, A. Stütz, A. Korshunov, Jüri Reimand, S. Schumacher and 125 more. Nature, 2012
871 citations recorded by the source corpus.
Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson’s disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/eb6b22a08d7e6744a6be8c5f155195a35151a558
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In Genetics
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Citations in the corpus
- Medulloblastomics: The End of the Beginning (2012, methodology): “*Subgroup frequency, demographics, clinical features and cytogenetic profiles were derived from a cohort of 827 medulloblastomas distributed into subgroups described by Northcott et al.(99).”
- Revisiting Global Gene Expression Analysis (2012, neutral): “…et al., 2000; Beer et al., 2002; Berger et al., 2010; Bhattacharjee et al., 2001; Bittner et al., 2000; Golub et al., 1999; Lapointe et al., 2004; Northcott et al., 2012; Ramaswamy et al., 2001; Ross et al., 2000; Schmitz et al., 2012; Shipp et al., 2002; Su et al., 2001; Cancer Genome Atlas,…”
- The whole-genome landscape of medulloblastoma subtypes (2017, positive): “A role for deregulated TGF β signalling in Group 3 has been suggested in our previous genomic/epigenomic studies 11,32 ; however, functional studies that further substantiate these observations are still lacking.”