| Literature DB >> 24336570 |
Brett E Johnson1, Tali Mazor1, Chibo Hong1, Michael Barnes2, Koki Aihara3,4, Cory Y McLean1, Shaun D Fouse1, Shogo Yamamoto3, Hiroki Ueda3, Kenji Tatsuno3, Saurabh Asthana5,6, Llewellyn E Jalbert7, Sarah J Nelson7,8, Andrew W Bollen2, W Clay Gustafson9, Elise Charron10, William A Weiss1,9,10, Ivan V Smirnov1, Jun S Song11,12, Adam B Olshen6,11, Soonmee Cha1, Yongjun Zhao13, Richard A Moore13, Andrew J Mungall13, Steven J M Jones13, Martin Hirst13, Marco A Marra13, Nobuhito Saito4, Hiroyuki Aburatani3, Akitake Mukasa4, Mitchel S Berger1, Susan M Chang1, Barry S Taylor5,6,11, Joseph F Costello1.
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.Entities:
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Year: 2013 PMID： 24336570 PMCID： PMC3998672 DOI： 10.1126/science.1239947
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728