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

Author:

Johnson Brett E.1,Mazor Tali1,Hong Chibo1,Barnes Michael2,Aihara Koki34,McLean Cory Y.1,Fouse Shaun D.1,Yamamoto Shogo3,Ueda Hiroki3,Tatsuno Kenji3,Asthana Saurabh56,Jalbert Llewellyn E.7,Nelson Sarah J.78,Bollen Andrew W.2,Gustafson W. Clay9,Charron Elise10,Weiss William A.1910,Smirnov Ivan V.1,Song Jun S.1112,Olshen Adam B.611,Cha Soonmee1,Zhao Yongjun13,Moore Richard A.13,Mungall Andrew J.13,Jones Steven J. M.13,Hirst Martin13,Marra Marco A.13,Saito Nobuhito4,Aburatani Hiroyuki3,Mukasa Akitake4,Berger Mitchel S.1,Chang Susan M.1,Taylor Barry S.5611,Costello Joseph F.1

Affiliation:

1. Department of Neurological Surgery, University of California, San Francisco, CA 94158, USA.

2. Department of Pathology, University of California, San Francisco, CA 94158, USA.

3. Genome Science Laboratory, Research Center for Advanced Science and Technology, University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan.

4. Department of Neurosurgery, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.

5. Department of Medicine, University of California, San Francisco, CA 94158, USA.

6. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158, USA.

7. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158, USA.

8. Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA.

9. Department of Pediatrics, University of California, San Francisco, CA 94158, USA.

10. Department of Neurology, University of California, San Francisco, CA 94158, USA.

11. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94158, USA.

12. Institute for Human Genetics, University of California, San Francisco, CA 94158, USA.

13. Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada.

Abstract

Back with a Vengeance After surgery, gliomas (a type of brain tumor) recur in nearly all patients and often in a more aggressive form. Johnson et al. (p. 189 , published online 12 December 2013) used exome sequencing to explore whether recurrent tumors harbor different mutations than the primary tumors and whether the mutational profile in the recurrences is influenced by postsurgical treatment of patients with temozolomide (TMZ), a chemotherapeutic drug known to damage DNA. In more than 40% of cases, at least half of the mutations in the initial glioma were undetected at recurrence. The recurrent tumors in many of the TMZ-treated patients bore the signature of TMZ-induced mutagenesis and appeared to follow an evolutionary path to high-grade glioma distinct from that in untreated patients.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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