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

• DOI: 10.1126/science.1239947
• Publication Date: 2013-12-13T02:31:13Z
• Authors: Brett E. Johnson; Tali Mazor; Chibo Hong; Michael Barnes; Koki Aihara; Cory Y. McLean; Shaun D. Fouse; Shogo Yamamoto; Hiroki Ueda; Kenji Tatsuno; Saurabh Asthana; Llewellyn E. Jalbert; Sarah J. Nelson; Andrew W. Bollen; W. Clay Gustafson; Elise Charron; William A. Weiss; Ivan V. Smirnov; Jun S. Song; Adam B. Olshen; Soonmee Cha; Yongjun Zhao; Richard A. Moore; Andrew J. Mungall; Steven J. M. Jones; Martin Hirst; Marco A. Marra; Nobuhito Saito; Hiroyuki Aburatani; Akitake Mukasa; Mitchel S. Berger; Susan M. Chang; Barry S. Taylor; Joseph F. Costello
• Keywords: Proto-Oncogene Proteins B-raf; X-linked Nuclear Protein; General Science & Technology; Clinical Sciences; Oncology and Carcinogenesis; DNA Mutational Analysis; 610; Antineoplastic Agents; 03 medical and health sciences; Rare Diseases; Cancer Genomics; Genetics; Temozolomide; Humans; Antineoplastic Agents, Alkylating; Cancer; 0303 health sciences; Biomedical and Clinical Sciences; Brain Neoplasms; TOR Serine-Threonine Kinases; Human Genome; Neurosciences; DNA Helicases; Brain; Nuclear Proteins; Glioma; Alkylating; Brain Disorders; 3. Good health; Brain Cancer; Dacarbazine; Orphan Drug; Good Health and Well Being; Neoplasm Recurrence; Local; Mutagenesis; Neoplasm Grading; Neoplasm Recurrence, Local; Tumor Suppressor Protein p53; Proto-Oncogene Proteins c-akt; Transcription Factors

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.