Abstract
The major known genetic contributor to meningioma formation was NF2, which is disrupted by mutation or loss in about 50% of tumors. Besides NF2, several recurrent driver mutations were recently uncovered through next-generation sequencing. Here, we performed whole-genome sequencing across 7 tumor-normal pairs to identify somatic genetic alterations in meningioma. As a result, Chromatin regulators, including multiple histone members, histone-modifying enzymes and several epigenetic regulators, are the major category among all of the identified copy number variants and single nucleotide variants. Notably, all samples contained copy number variants in histone members. Recurrent chromosomal rearrangements were detected on chromosome 22q, 6p21-p22 and 1q21, and most of the histone copy number variants occurred in these regions. These results will help to define the genetic landscape of meningioma and facilitate more effective genomics-guided personalized therapy.
Highlights
Meningiomas are the most common primary intracranial neoplasms in adults, accounting for 35.8% of all primary central nervous system (CNS) tumors diagnosed in the US [1, 2]
A total of 393,678 somatic single nucleotide variants (SNVs) were identified through whole-genome sequencing of the seven paired meningioma samples, including 103,289 inserted and deleted sequences and 290,389 single nucleotide polymorphisms (SNPs) (Supplementary Table 1 and 2)
Through analyzing the distribution of somatic mutations across individual chromosome, SNVs were more commonly found on chromosome 1, 3, 9 and 19, while chromosome 22, 2 and 6 carried more copy number variants (CNVs) (Figure 1C, 1D)
Summary
Meningiomas are the most common primary intracranial neoplasms in adults, accounting for 35.8% of all primary central nervous system (CNS) tumors diagnosed in the US [1, 2]. In China, meningiomas were the second most common CNS tumors, constituting 14.06% of all primary intracranial tumors [3]. The only genetic driver of meningiomas to be identified was bi-allelic mutation or loss of the tumor suppressor gene neurofibromatosis 2 (NF2) on chromosome 22, encoding the protein Merlin. With the development of next-generation of sequencing, several recent studies have reported new driver mutations, including TRAF7, KLF4, AKT1, SMO, PIK3CA, NOTCH2, SMARCB1, CHEK2, SMARCE1 and POLR2A, in the remaining half of meningiomas with wild-type NF2 [8, 9, 10, 11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
