Immunohistochemistry of a glioblastoma tumor specimen with monoclonal antibodies specific for the mismatch repair protein MSH6. Loss of MSH6 is found in recurrent glioblastomas and is associated with the progressive growth of these tumors while they are under treatment with the alkylating chemotherapeutic agent temozolomide. Because mismatch repair deficiency is known to mediate alkylator drug resistance in vitro, and temozolomide is a component of the standard-of-care treatment for glioblastoma, the finding of MSH6 loss in glioblastoma recurrences links the well-established in vitro phenomenon to the most common clinical treatment scenario encountered in the care of neuro-oncology patients. For further details, please see Cahill et al. on page 2038 of this issue.

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