American Association for Cancer Research
21598290cd160575-sup-166719_2_supp_3679084_9dz111.xls (42.5 kB)

Supplementary Table S5 from Immunogenomics of Hypermutated Glioblastoma: A Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy

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posted on 2023-04-03, 21:02 authored by Tanner M. Johanns, Christopher A. Miller, Ian G. Dorward, Christina Tsien, Edward Chang, Arie Perry, Ravindra Uppaluri, Cole Ferguson, Robert E. Schmidt, Sonika Dahiya, George Ansstas, Elaine R. Mardis, Gavin P. Dunn

DNA repair pathway mutations found in the founding clone (Cluster 1). Gene list was derived from, and annotated with data from ClinVar (, COSMIC, the Foundation Medicine report provided to this patient, and SIFT/PolyPhen predictions from ExAC (



Washington University School of Medicine

Genome Institute



We present the case of a patient with a left frontal glioblastoma with primitive neuroectodermal tumor features and hypermutated genotype in the setting of a POLE germline alteration. During standard-of-care chemoradiation, the patient developed a cervical spine metastasis and was subsequently treated with pembrolizumab. Shortly thereafter, the patient developed an additional metastatic spinal lesion. Using whole-exome DNA sequencing and clonal analysis, we report changes in the subclonal architecture throughout treatment. Furthermore, a persistently high neoantigen load was observed within all tumors. Interestingly, following initiation of pembrolizumab, brisk lymphocyte infiltration was observed in the subsequently resected metastatic spinal lesion and an objective radiographic response was noted in a progressive intracranial lesion, suggestive of active central nervous system (CNS) immunosurveillance following checkpoint blockade therapy.Significance: It is unclear whether hypermutated glioblastomas are susceptible to checkpoint blockade in adults. Herein, we provide proof of principle that glioblastomas with DNA-repair defects treated with checkpoint blockade may result in CNS immune activation, leading to clinically and immunologically significant responses. These patients may represent a genomically stratified group for whom immunotherapy could be considered. Cancer Discov; 6(11); 1230–6. ©2016 AACR.See related commentary by Snyder and Wolchok, p. 1210.This article is highlighted in the In This Issue feature, p. 1197

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