Supplementary Table S4 from Clinical and Genomic Predictors of Adverse Events in Newly Diagnosed Glioblastoma

Lim-Fat, Mary Jane; Iorgulescu, J. Bryan; Rahman, Rifaquat; Bhave, Varun; Muzikansky, Alona; Woodward, Eleanor; Whorral, Sydney; Allen, Marie; Touat, Mehdi; Li, Xiaomei; Xy, Gongwen; Patel, Jay; Gerstner, Elizabeth R.; Kalpathy-Cramer, Jayashree; Youssef, Gilbert; Chukwueke, Ugonma; McFaline-Figueroa, J. Ricardo; Nayak, Lakshmi; Lee, Eudocia Q.; Reardon, David A.; Beroukhim, Rameen; Huang, Raymond Y.; Bi, Wenya Linda; Ligon, Keith L.; Wen, Patrick Y.

doi:10.1158/1078-0432.25515886.v1

ccr-23-3018_supplementary_table_s4_suppts4.docx (44.21 kB)

Supplementary Table S4 from Clinical and Genomic Predictors of Adverse Events in Newly Diagnosed Glioblastoma

journal contribution

posted on 2024-04-01, 07:23 authored by Mary Jane Lim-Fat, J. Bryan Iorgulescu, Rifaquat Rahman, Varun Bhave, Alona Muzikansky, Eleanor Woodward, Sydney Whorral, Marie Allen, Mehdi Touat, Xiaomei Li, Gongwen Xy, Jay Patel, Elizabeth R. Gerstner, Jayashree Kalpathy-Cramer, Gilbert Youssef, Ugonma Chukwueke, J. Ricardo McFaline-Figueroa, Lakshmi Nayak, Eudocia Q. Lee, David A. Reardon, Rameen Beroukhim, Raymond Y. Huang, Wenya Linda Bi, Keith L. Ligon, Patrick Y. Wen

Supplemental Table 4: Multivariable analysis of molecular alterations associated with seizure at presentation showing significant genes at a false discovery rate (FDR) <0.2. Multivariable models included preoperative tumor volume, tumor location, and age at diagnosis. Abbreviations: GoF, gain of function; LoF, loss of function.

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ARTICLE ABSTRACT

Adverse clinical events cause significant morbidity in patients with GBM (GBM). We examined whether genomic alterations were associated with AE (AE) in patients with GBM. We identified adults with histologically confirmed IDH-wild-type GBM with targeted next-generation sequencing (OncoPanel) at Dana Farber Cancer Institute from 2013 to 2019. Seizure at presentation, lymphopenia, thromboembolic events, pseudoprogression, and early progression (within 6 months of diagnosis) were identified as AE. The biologic function of genetic variants was categorized as loss-of-function (LoF), no change in function, or gain-of-function (GoF) using a somatic tumor mutation knowledge base (OncoKB) and consensus protein function predictions. Associations between functional genomic alterations and AE were examined using univariate logistic regressions and multivariable regressions adjusted for additional clinical predictors. Our study included 470 patients diagnosed with GBM who met the study criteria. We focused on 105 genes that had sequencing data available for ≥ 90% of the patients and were altered in ≥10% of the cohort. Following false-discovery rate (FDR) correction and multivariable adjustment, the TP53, RB1, IGF1R, and DIS3 LoF alterations were associated with lower odds of seizures, while EGFR, SMARCA4, GNA11, BRD4, and TCF3 GoF and SETD2 LoF alterations were associated with higher odds of seizures. For all other AE of interest, no significant associations were found with genomic alterations following FDR correction. Genomic biomarkers based on functional variant analysis of a routine clinical panel may help identify AE in GBM, particularly seizures. Identifying these risk factors could improve the management of patients through better supportive care and consideration of prophylactic therapies.