Mutational Analysis Reveals the Origin and Therapy-Driven Evolution of Recurrent Glioma.

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Bibliographic Details
Title:	Mutational Analysis Reveals the Origin and Therapy-Driven Evolution of Recurrent Glioma.
Authors:	Johnson, Brett E., Mazor, Tali, Chibo Hong, Barnes, Michael, Koki Aihara, McLean, Cory Y., Fouse, Shaun D., Shogo Yamamoto, Hiroki Ueda, Kenji Tatsuno, Asthana, Saurabh, Jalbert, Llewellyn E., Nelson, Sarah J., Bollen, Andrew W., Gustafson, W. Clay, Charron, Elise, Weiss, William A., Smirnov, Ivan V., Song, Jun S., Olshen, Adam B.
Source:	Science (pre-March 2025). 1/10/2014, Vol. 343 Issue 6167, p189-193. 5p.
Subjects:	Gliomas, Tumors, Genetic mutation, Cancer relapse, Temozolomide, Retinoblastoma gene, Rapamycin, Mutagenesis
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 exornes 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. [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection

Description
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 exornes 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. [ABSTRACT FROM AUTHOR]
ISSN:	00368075
DOI:	10.1126/science.1239947