Mechanisms of TMZ-associated Hypermutation in Glioma

Tumor recurrence is the leading cause of cancer mortality. We have shown that low-grade gliomas treated with the chemotherapeutic drug temozolomide follow an alternative evolutionary path to glioblastoma. Upon recurrence, these TMZ-treated tumors were hypermutated and harbored driver mutations in key tumor suppressors and oncogenes. We are currently researching the mechanism driving hypermutation in glioma and developing model systems to study somatic hypermutation.

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Johnson BE*, Mazor T*, Hong C, Barnes M, Aihara K, McLean CY, Fouse SD, Yamamoto S, Ueda H, Tatsuno K, Asthana S, Jalbert LE, Nelson SJ, Bollen AW, Gustafson WC, Charron E, Weiss WA, Smirnov IV, Song JS, Olshen AB, Cha S, Zhao Y, Moore RA, Mungall AJ, Jones SJ, Hirst M, Marra MA, Saito N, Aburatani H, Mukasa A, Berger MS, Chang SM, Taylor BS, Costello JF. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science. 2014 Jan 10; 343(6167):189-93.

Who works on this project in the Costello Lab?