Mutational Analysis of Recurrent Meningioma Progressing From Atypical to Rhabdoid Subtype

作者：Bujko Mateusz^*; Machnicki Marcin M; Grecka Emilia; Rusetska Nataliia; Matyja Ewa; Kober Paulina; Mandat Tomasz; Rydzanicz Malgorzata; Ploski Rafal; Krajewski Romuald; Bonicki Wieslaw; Stoklosa Tomasz; Siedlecki Janusz A

来源：World Neurosurgery, 2017, 97: UNSP 754.e1.

DOI：10.1016/j.wneu.2016.10.047

• Anaplastic
• Atypical
• Meningioma
• Progression
• Rhabdoid
• Somatic mutation

BACKGROUND: Rhabdoid meningioma is rare aggressive meningioma histological subtype that develops predominantly through progression from less malignant tumors. Owing to its low incidence, this tumor's biological background is unknown. The aim of this study was to profile somatic mutations in 4 meningioma samples from the same patient, derived previously from 4 subsequent tumor resections.
CASE DESCRIPTION: A 58-year-old woman presented with recurrent meningioma progressing from atypical to rhabdoid subtype. Four tumor samples that represent a primary tumor (atypical GII) and 3 recurrent tumors that were subsequently removed (anaplastic GIII, rhabdoid GIII, and anaplastic/rhabdoid GIII) from this patient were subjected to mutational analysis of coding sequences of 952 tumor-related genes. Three mutations were identified in all tumor samples exhibiting a high allelic frequency: ARID1A frameshift deletion, NF2 in-frame deletion, and missense variant of SRSF2. The predicted inactivating effect of ARID1A deletion was confirmed by immunohistochemical staining of tumor sections in which a high proportion of cells lacked protein expression. Additional low-allelic-fraction mutations were observed in all tumor samples, likely representing "passenger," low-effect mutations that reflect a clonal selection of tumor cells through malignant progression of the meningioma.
CONCLUSION: The mutation of ARID1A that encodes the subunit of the SWI/SNF complex represents the most likely driver of the tumor's malignant potential. It also may be involved in the acquisition of the rhabdoid phenotype, given that mutations in chromatin remodeling proteins are the hallmark of atypical teratoid/rhabdoid tumors.

• 出版日期2017-1