Genomic Analysis of Non- NF2 Meningiomas Reveals Mutations in TRAF7 , KLF4 , AKT1 , and SMO

Author:

Clark Victoria E.1,Erson-Omay E. Zeynep1,Serin Akdes1,Yin Jun2,Cotney Justin2,Özduman Koray3,Avşar Timuçin4,Li Jie5,Murray Phillip B.1,Henegariu Octavian1,Yilmaz Saliha1,Günel Jennifer Moliterno6,Carrión-Grant Geneive1,Yılmaz Baran7,Grady Conor1,Tanrıkulu Bahattin7,Bakırcıoğlu Mehmet1,Kaymakçalan Hande8,Caglayan Ahmet Okay1,Sencar Leman1,Ceyhun Emre1,Atik A. Fatih7,Bayri Yaşar7,Bai Hanwen1,Kolb Luis E.1,Hebert Ryan M.1,Omay S. Bulent1,Mishra-Gorur Ketu1,Choi Murim2,Overton John D.9,Holland Eric C.10,Mane Shrikant29,State Matthew W.11,Bilgüvar Kaya1,Baehring Joachim M.12,Gutin Philip H.6,Piepmeier Joseph M.13,Vortmeyer Alexander5,Brennan Cameron W.14,Pamir M. Necmettin3,Kılıç Türker15,Lifton Richard P.216,Noonan James P.217,Yasuno Katsuhito1,Günel Murat118

Affiliation:

1. Departments of Neurosurgery and Genetics, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT 06510, USA.

2. Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.

3. Department of Neurosurgery, Acibadem University School of Medicine, Istanbul 34848, Turkey.

4. Dr. Orhan Öcalgiray Molecular Biology-Biotechnology and Genetics Research Center, Istanbul Technical University, Maslak 34469, Istanbul, Turkey.

5. Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA.

6. Department of Neurosurgery and Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

7. Department of Neurosurgery, Marmara University School of Medicine, Istanbul 34854, Turkey.

8. Department of Genetics and Bioinformatics, Bahcesehir University, Istanbul 34353, Turkey.

9. Center for Genome Analysis, Yale School of Medicine, West Haven, CT 06516, USA.

10. Departments of Cancer Biology and Genetics, Neurosurgery, Neurology, and Surgery, Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

11. Departments of Genetics and Psychiatry, Yale Program on Neurogenetics and Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.

12. Departments of Neurology, Neurosurgery, and Internal Medicine, Yale Program in Brain Tumor Research and Yale Brain Tumor Center, Yale School of Medicine, New Haven, CT 06510, USA.

13. Department of Neurosurgery, Yale Program in Brain Tumor Research and Yale Brain Tumor Center, Yale School of Medicine, New Haven, CT 06510, USA.

14. Department of Neurosurgery and Brain Tumor Center, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

15. Department of Neurosurgery, Bahcesehir University School of Medicine, Istanbul 34349 Turkey.

16. Department of Internal Medicine, Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06510, USA.

17. Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06520, USA.

18. Yale Program on Neurogenetics, Yale School of Medicine, New Haven, CT 06510, USA.

Abstract

Genetic Clues to Meningioma Meningiomas are the most common primary brain tumors in adults. Located within the layer of tissue covering the brain, these tumors are usually slow-growing and benign but can cause serious neurological complications. About half of these tumors have mutations in the neurofibromin 2 gene ( NF2 ). To identify other genes that contribute to meningioma pathogenesis, Clark et al. (p. 1077 , published online 24 January) performed genome sequence analysis on 300 tumors. Meningiomas fell into two general classes: benign tumors located at the skull base—which tend to harbor mutations in the TRAF7, KLF4, AKT1 , and SMO genes—and higher-grade tumors located in the cerebral and cerebellar hemispheres harbor mutations in NF2.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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