Genomic copy number variation correlates with survival outcomes in WHO grade IV glioma

Zachary S. Buchwald; Sibo Tian; Michael Rossi; Geoffrey H. Smith; Jeffrey Switchenko; Jennifer E. Hauenstein; Carlos S. Moreno; Robert H. Press; Roshan S. Prabhu; Jim Zhong; Debra F. Saxe; Stewart G. Neill; Jeffrey J. Olson; Ian R. Crocker; Walter J. Curran; Hui Kuo G. Shu

doi:10.1038/s41598-020-63789-9

Genomic copy number variation correlates with survival outcomes in WHO grade IV glioma

Zachary S. Buchwald, Sibo Tian, Michael Rossi, Geoffrey H. Smith, Jeffrey Switchenko, Jennifer E. Hauenstein, Carlos S. Moreno, Robert H. Press, Roshan S. Prabhu, Jim Zhong, Debra F. Saxe, Stewart G. Neill, Jeffrey J. Olson, Ian R. Crocker, Walter J. Curran, Hui Kuo G. Shu

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Abstract

Allele-specific copy number analysis of tumors (ASCAT) assesses copy number variations (CNV) while accounting for aberrant cell fraction and tumor ploidy. We evaluated if ASCAT-assessed CNV are associated with survival outcomes in 56 patients with WHO grade IV gliomas. Tumor data analyzed by Affymetrix OncoScan FFPE Assay yielded the log ratio (R) and B-allele frequency (BAF). Input into ASCAT quantified CNV using the segmentation function to measure copy number inflection points throughout the genome. Quantified CNV was reported as log R and BAF segment counts. Results were confirmed on The Cancer Genome Atlas (TCGA) glioblastoma dataset. 25 (44.6%) patients had MGMT hyper-methylated tumors, 6 (10.7%) were IDH1 mutated. Median follow-up was 36.4 months. Higher log R segment counts were associate with longer progression-free survival (PFS) [hazard ratio (HR) 0.32, p < 0.001], and overall survival (OS) [HR 0.45, p = 0.01], and was an independent predictor of PFS and OS on multivariable analysis. Higher BAF segment counts were linked to longer PFS (HR 0.49, p = 0.022) and OS (HR 0.49, p = 0.052). In the TCGA confirmation cohort, longer 12-month OS was seen in patients with higher BAF segment counts (62.3% vs. 51.9%, p = 0.0129) and higher log R (63.6% vs. 55.2%, p = 0.0696). Genomic CNV may be a novel prognostic biomarker for WHO grade IV glioma patient outcomes.

Original language	English
Article number	7355
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-63789-9
State	Published - 1 Dec 2020
Externally published	Yes

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Buchwald, Z. S., Tian, S., Rossi, M., Smith, G. H., Switchenko, J., Hauenstein, J. E., Moreno, C. S., Press, R. H., Prabhu, R. S., Zhong, J., Saxe, D. F., Neill, S. G., Olson, J. J., Crocker, I. R., Curran, W. J., & Shu, H. K. G. (2020). Genomic copy number variation correlates with survival outcomes in WHO grade IV glioma. Scientific Reports, 10(1), Article 7355. https://doi.org/10.1038/s41598-020-63789-9

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title = "Genomic copy number variation correlates with survival outcomes in WHO grade IV glioma",

abstract = "Allele-specific copy number analysis of tumors (ASCAT) assesses copy number variations (CNV) while accounting for aberrant cell fraction and tumor ploidy. We evaluated if ASCAT-assessed CNV are associated with survival outcomes in 56 patients with WHO grade IV gliomas. Tumor data analyzed by Affymetrix OncoScan FFPE Assay yielded the log ratio (R) and B-allele frequency (BAF). Input into ASCAT quantified CNV using the segmentation function to measure copy number inflection points throughout the genome. Quantified CNV was reported as log R and BAF segment counts. Results were confirmed on The Cancer Genome Atlas (TCGA) glioblastoma dataset. 25 (44.6%) patients had MGMT hyper-methylated tumors, 6 (10.7%) were IDH1 mutated. Median follow-up was 36.4 months. Higher log R segment counts were associate with longer progression-free survival (PFS) [hazard ratio (HR) 0.32, p < 0.001], and overall survival (OS) [HR 0.45, p = 0.01], and was an independent predictor of PFS and OS on multivariable analysis. Higher BAF segment counts were linked to longer PFS (HR 0.49, p = 0.022) and OS (HR 0.49, p = 0.052). In the TCGA confirmation cohort, longer 12-month OS was seen in patients with higher BAF segment counts (62.3% vs. 51.9%, p = 0.0129) and higher log R (63.6% vs. 55.2%, p = 0.0696). Genomic CNV may be a novel prognostic biomarker for WHO grade IV glioma patient outcomes.",

author = "Buchwald, {Zachary S.} and Sibo Tian and Michael Rossi and Smith, {Geoffrey H.} and Jeffrey Switchenko and Hauenstein, {Jennifer E.} and Moreno, {Carlos S.} and Press, {Robert H.} and Prabhu, {Roshan S.} and Jim Zhong and Saxe, {Debra F.} and Neill, {Stewart G.} and Olson, {Jeffrey J.} and Crocker, {Ian R.} and Curran, {Walter J.} and Shu, {Hui Kuo G.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41598-020-63789-9",

language = "English",

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T1 - Genomic copy number variation correlates with survival outcomes in WHO grade IV glioma

AU - Buchwald, Zachary S.

AU - Tian, Sibo

AU - Rossi, Michael

AU - Smith, Geoffrey H.

AU - Switchenko, Jeffrey

AU - Hauenstein, Jennifer E.

AU - Moreno, Carlos S.

AU - Press, Robert H.

AU - Prabhu, Roshan S.

AU - Zhong, Jim

AU - Saxe, Debra F.

AU - Neill, Stewart G.

AU - Olson, Jeffrey J.

AU - Crocker, Ian R.

AU - Curran, Walter J.

AU - Shu, Hui Kuo G.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Allele-specific copy number analysis of tumors (ASCAT) assesses copy number variations (CNV) while accounting for aberrant cell fraction and tumor ploidy. We evaluated if ASCAT-assessed CNV are associated with survival outcomes in 56 patients with WHO grade IV gliomas. Tumor data analyzed by Affymetrix OncoScan FFPE Assay yielded the log ratio (R) and B-allele frequency (BAF). Input into ASCAT quantified CNV using the segmentation function to measure copy number inflection points throughout the genome. Quantified CNV was reported as log R and BAF segment counts. Results were confirmed on The Cancer Genome Atlas (TCGA) glioblastoma dataset. 25 (44.6%) patients had MGMT hyper-methylated tumors, 6 (10.7%) were IDH1 mutated. Median follow-up was 36.4 months. Higher log R segment counts were associate with longer progression-free survival (PFS) [hazard ratio (HR) 0.32, p < 0.001], and overall survival (OS) [HR 0.45, p = 0.01], and was an independent predictor of PFS and OS on multivariable analysis. Higher BAF segment counts were linked to longer PFS (HR 0.49, p = 0.022) and OS (HR 0.49, p = 0.052). In the TCGA confirmation cohort, longer 12-month OS was seen in patients with higher BAF segment counts (62.3% vs. 51.9%, p = 0.0129) and higher log R (63.6% vs. 55.2%, p = 0.0696). Genomic CNV may be a novel prognostic biomarker for WHO grade IV glioma patient outcomes.

AB - Allele-specific copy number analysis of tumors (ASCAT) assesses copy number variations (CNV) while accounting for aberrant cell fraction and tumor ploidy. We evaluated if ASCAT-assessed CNV are associated with survival outcomes in 56 patients with WHO grade IV gliomas. Tumor data analyzed by Affymetrix OncoScan FFPE Assay yielded the log ratio (R) and B-allele frequency (BAF). Input into ASCAT quantified CNV using the segmentation function to measure copy number inflection points throughout the genome. Quantified CNV was reported as log R and BAF segment counts. Results were confirmed on The Cancer Genome Atlas (TCGA) glioblastoma dataset. 25 (44.6%) patients had MGMT hyper-methylated tumors, 6 (10.7%) were IDH1 mutated. Median follow-up was 36.4 months. Higher log R segment counts were associate with longer progression-free survival (PFS) [hazard ratio (HR) 0.32, p < 0.001], and overall survival (OS) [HR 0.45, p = 0.01], and was an independent predictor of PFS and OS on multivariable analysis. Higher BAF segment counts were linked to longer PFS (HR 0.49, p = 0.022) and OS (HR 0.49, p = 0.052). In the TCGA confirmation cohort, longer 12-month OS was seen in patients with higher BAF segment counts (62.3% vs. 51.9%, p = 0.0129) and higher log R (63.6% vs. 55.2%, p = 0.0696). Genomic CNV may be a novel prognostic biomarker for WHO grade IV glioma patient outcomes.

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DO - 10.1038/s41598-020-63789-9

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SN - 2045-2322

VL - 10

JO - Scientific Reports

JF - Scientific Reports

IS - 1

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ER -

Genomic copy number variation correlates with survival outcomes in WHO grade IV glioma

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