Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma
نویسندگان
چکیده
Abstract Tumor recurrence is a leading cause of cancer mortality. Therapies for recurrent disease may fail, at least in part, because the genomic alterations driving the growth of recurrences are distinct from those in the initial tumor. To explore this hypothesis, we sequenced the exomes of 23 initial low-grade gliomas and recurrent tumors resected from the same patients. In 43% of cases, at least half of the mutations in the initial tumor were undetected at recurrence, including driver mutations in TP53, ATRX, SMARCA4, and BRAF; this suggests that recurrent tumors are often seeded by cells derived from the initial tumor at a very early stage of their evolution. Notably, tumors from 6 of 10 patients treated with the chemotherapeutic drug temozolomide (TMZ) followed an alternative evolutionary path to high-grade glioma. At recurrence, these tumors were hypermutated and harbored driver mutations in the RB (retinoblastoma) and Akt-mTOR (mammalian target of rapamycin) pathways that bore the signature of TMZ-induced mutagenesis.
منابع مشابه
Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma.
Tumor recurrence is a leading cause of cancer mortality. Therapies for recurrent disease may fail, at least in part, because the genomic alterations driving the growth of recurrences are distinct from those in the initial tumor. To explore this hypothesis, we sequenced the exomes of 23 initial low-grade gliomas and recurrent tumors resected from the same patients. In 43% of cases, at least half...
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متن کاملA phase I/II clinical trial for adult recurrent glioma using 131i-tm-601, an iodinated peptide derived from scorpion venom
131I-TM-601 is a 36-amino acid peptide, called chlorotoxin (TM-601), derived from scorpion venom labeled with I-131. TM-601 binds a receptor on the surface of tumor cells, and not on normal cells. A single dose of 131I-TM-601 administered intracranially to human xenografted mouse models of glioma has been shown to extend survival up to 269% in multiple studies. 131I-TM-601 is in a multi-center ...
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تاریخ انتشار 2015