Department of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
Virchows Arch. 2013 Feb;462(2):211-7. doi: 10.1007/s00428-012-1342-8. Epub 2012 Dec 8.
Sporadic vestibular schwannomas are benign tumors originating from the Schwann cells of the vestibular portion of the eigth cranial nerve. An important clinical hallmark of these tumors is their variable growth rate. Investigating vestibular schwannoma biology can help to clarify this variable growth rate and may offer targets for therapeutic treatment. A recent mutation analysis on sporadic non-head and neck schwannomas detected BRAF mutations in around 20 % of tumors. BRAF is part of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. MAPK/ERK activation is associated with an uncontrolled cell growth. Mutated BRAF can function as a target to inhibit this pathway. Mutations in BRAF and other members of the MAPK/ERK pathway have not been investigated in sporadic vestibular schwannomas before. The goal of this study was to investigate if these mutations are present in vestibular schwannomas and whether these mutations correlate with tumor growth. Tumor specimens of 48 patients surgically treated for a sporadic vestibular schwannoma were analyzed. An allele-specific quantitative real-time PCR assay was performed to detect the 13 most frequent mutations affecting BRAF, EGFR, PIK3CA, and KRAS. Radiologically measured tumor growth was included in the analysis to identify potential relationships between these mutations and tumor progression. No activating hotspot mutations in BRAF, EGFR, PIK3CA, or KRAS were detected. The 13 most frequent mutations affecting BRAF, EGFR, PIK3CA, and KRAS are not involved in sporadic vestibular schwannoma development. These results are in contrast to the recent detection of these BRAF mutations in non-head and neck schwannomas.
散发性前庭神经鞘瘤是起源于第八颅神经前庭部分施旺细胞的良性肿瘤。这些肿瘤的一个重要临床特征是其生长速度的可变性。研究前庭神经鞘瘤的生物学特性可以帮助阐明这种可变的生长速度，并可能为治疗提供靶点。最近对散发性非头颈部神经鞘瘤的突变分析检测到大约 20%的肿瘤存在 BRAF 突变。BRAF 是丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）通路的一部分。MAPK/ERK 激活与不受控制的细胞生长有关。突变的 BRAF 可以作为抑制该途径的靶点。BRAF 和 MAPK/ERK 通路的其他成员的突变在前庭神经鞘瘤中尚未被研究。本研究的目的是研究这些突变是否存在于前庭神经鞘瘤中，以及这些突变是否与肿瘤生长相关。对 48 例接受手术治疗的散发性前庭神经鞘瘤患者的肿瘤标本进行了分析。采用等位基因特异性定量实时 PCR 法检测影响 BRAF、EGFR、PIK3CA 和 KRAS 的 13 种最常见的突变。对影像学测量的肿瘤生长进行了分析，以确定这些突变与肿瘤进展之间的潜在关系。未检测到 BRAF、EGFR、PIK3CA 或 KRAS 的激活热点突变。影响 BRAF、EGFR、PIK3CA 和 KRAS 的 13 种最常见的突变不参与散发性前庭神经鞘瘤的发生。这些结果与最近在非头颈部神经鞘瘤中检测到这些 BRAF 突变形成对比。
