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Comprehensive genetic alteration profiling in primary and recurrent glioblastoma

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Glioblastoma (GBM) is heterogeneous and underlying genomic profiles influence evolution, resistance, and therapeutic responses. While extensive knowledge regarding genomic profiling of primary GBM exists, there remains a lack of understanding of genomic differences in recurrent GBM.


We used the FoundationOne® comprehensive genomic profiling assay (CGP) to analyze ten matched primary and recurrent GBM. Genomic alterations (GA) were compared to the cancer database Catalogue of Somatic Mutations in Cancer (COSMIC).


All matched tumor pairs demonstrated differences in GA between the primary and recurrence including one resected without any intervening therapy. This suggests that time and/or therapeutic intervention contribute to GA. Although mutations were common to both the primary and recurrence, the percent reads varied substantially suggesting clonal expansions and contractions. For example, EGFR mutations were significantly expanded in three patients, and CNAs were increased in two patients at recurrence. Four genes that were commonly altered in both primary and recurrent GBM were more prevalent in our cohort than reported in COSMIC: CDKN2A (86% vs. 53%) and CDKN2B (86% vs. 54%) deletions, EGFR activating mutation (52% vs. 10%) or amplification (81% vs. 45%), and TERT mutation (95% vs. 51%). Lastly, PI3K pathway activating mutations were also commonly seen in our cohort (67%).


CGP revealed that GA identified in GBM changed over time and with treatment. Mutations in TERT, CDKN2A/CDKN2B, EGFR, and PI3K pathway were commonly observed in both primary and recurrent GBM revealing their prognostic and therapeutic potential. This may have important implications for individualized therapies and needs further evaluation.

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We acknowledge Foundation Medicine for performing the FoundationOne® comprehensive genomic profiling in this investigator initiated study.


This work was supported by NCI F30 CA203397 to B.K.N. The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication.

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Correspondence to Michele R. Aizenberg.

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The authors declare that there is no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors. This study was deemed exempt by the UNMC Institutional Review Board and the Fred and Pamela Buffet Cancer Center Scientific Review Committee as all patients included are deceased. Approval for this study, including a waiver of informed consent and a HIPAA waiver of authorization, was also obtained from the Western Institutional Review Board (Protocol No. 20152817).

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Neilsen, B.K., Sleightholm, R., McComb, R. et al. Comprehensive genetic alteration profiling in primary and recurrent glioblastoma. J Neurooncol 142, 111–118 (2019).

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