2017
DOI: 10.1093/neuonc/nox232
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Biological and therapeutic implications of multisector sequencing in newly diagnosed glioblastoma

Abstract: The substantial spatial heterogeneity observed in different GBM tumor sectors, especially in spatially restricted hypermutator cases, raises important caveats to our current dependence on single-sector molecular information to guide either targeted or immune-based treatments.

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Cited by 43 publications
(41 citation statements)
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“…26 But even within the same untreated tumor, areas of hypermutation can be identified, as described very recently. 27 The different GBM models now available to us can be valuable tools for studying corresponding human GBMs with comparable mutational burdens and their response to therapy with ICB or in combination with other treatment modalities such as chemo-radiotherapy. [24][25][26]50 The results of our study highlight the value of different GBM models for recapitulating different types of immune interactions likely in different human gliomas.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…26 But even within the same untreated tumor, areas of hypermutation can be identified, as described very recently. 27 The different GBM models now available to us can be valuable tools for studying corresponding human GBMs with comparable mutational burdens and their response to therapy with ICB or in combination with other treatment modalities such as chemo-radiotherapy. [24][25][26]50 The results of our study highlight the value of different GBM models for recapitulating different types of immune interactions likely in different human gliomas.…”
Section: Discussionmentioning
confidence: 99%
“…20,23 Human GBM is mainly considered not highly mutated, even if cases of hypermutated GBM are described, as with POLE deficiency, biallelic mismatch repair deficiency, or even within areas of the same tumor. [24][25][26][27] Based on this current knowledge of human GBM, some mouse models are starting to be analyzed for the same critical features.…”
Section: Introductionmentioning
confidence: 99%
“…Genetic analysis of small biopsy specimens may not reflect intratumor heterogeneity or uncover mutations only present at a specific metastatic site (Gerlinger et al, 2012). Intratumoral heterogeneity is defined by the presence of different mutations in different parts of the same tumor and is a well-known feature of high-grade glioma (Sottoriva et al, 2013;Aubry et al, 2015;Mahlokozera et al, 2017) and medulloblastoma (Morrissy et al, 2017). A study of 10 patients with newly diagnosed glioblastoma whose tumors were sequenced in different sectors demonstrated that 51% of mutations were clonal (present in all tumor cells), 3% were subclonal (present in a subset of tumor cells) but shared between different sectors, and that 46% of mutations were subclonal and unique to a particular sector.…”
Section: Csf-derived Cfdna Offers Additional Genetic Information Beyomentioning
confidence: 99%
“…A study of 10 patients with newly diagnosed glioblastoma whose tumors were sequenced in different sectors demonstrated that 51% of mutations were clonal (present in all tumor cells), 3% were subclonal (present in a subset of tumor cells) but shared between different sectors, and that 46% of mutations were subclonal and unique to a particular sector. Moreover, 80% of patients had potentially targetable mutations that were not shared between sectors, which highlights the danger of relying on single-sector sequencing information (Mahlokozera et al, 2017).…”
Section: Csf-derived Cfdna Offers Additional Genetic Information Beyomentioning
confidence: 99%
“…Accumulated evidence shows high intratumoral heterogeneity (ITH) of GBM. [5][6][7] Actually, gliomas are typically heterogeneous mixtures of genetic subclones. The evolution of glioma cells can be viewed as a Darwinian process, in which tumor microenvironment (such as treatment) ablates vulnerable cells and positively selects for resistant subclones.…”
mentioning
confidence: 99%