Immunogenomics of Hypermutated Glioblastoma: a Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy.

Cancer Discov. 2016 Sep 28. pii: CD-16-0575. [Epub ahead of print]


We present the case of a patient with a left frontal glioblastoma with PNET 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 CNS immunosurveillance following checkpoint blockade therapy.


Johanns TM1, Miller CA2, Dorward IG3, Tsien C4, Chang E5, Perry A5, Uppaluri R6, Ferguson C7, Schmidt RE7, Dahiya S7, Ansstas G1, Mardis ER8, Dunn GP9.

Institute Authors

Chris Miller, Ph.D.