Abedalthagafi Malak S, Merrill Parker H, Bi Wenya Linda, Jones Robert T, Listewnik Marc L, Ramkissoon Shakti H, Thorner Aaron R, Dunn Ian F, Beroukhim Rameen, Alexander Brian M, Brastianos Priscilla K, Francis Joshua M, Folkerth Rebecca D, Ligon Keith L, Van Hummelen Paul, Ligon Azra H, Santagata Sandro
Department of Pathology, Division of Neuropathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Oncotarget. 2014 Nov 15;5(21):10596-606. doi: 10.18632/oncotarget.2517.
Meningiomas are a diverse group of tumors with a broad spectrum of histologic features. There are over 12 variants of meningioma, whose genetic features are just beginning to be described. Angiomatous meningioma is a World Health Organization (WHO) meningioma variant with a predominance of blood vessels. They are uncommon and confirming the histopathologic classification can be challenging. Given a lack of biomarkers that define the angiomatous subtype and limited understanding of the genetic changes underlying its tumorigenesis, we compared the genomic characteristics of angiomatous meningioma to more common meningioma subtypes. While typical grade I meningiomas demonstrate monosomy of chromosome 22 or lack copy number aberrations, 13 of 14 cases of angiomatous meningioma demonstrated a distinct copy number profile--polysomies of at least one chromosome, but often of many, especially in chromosomes 5, 13, and 20. WHO grade II atypical meningiomas with angiomatous features have both polysomies and genetic aberrations characteristic of other atypical meningiomas. Sequencing of over 560 cancer-relevant genes in 16 cases of angiomatous meningioma showed that these tumors lack common mutations found in other variants of meningioma. Our study demonstrates that angiomatous meningiomas have distinct genomic features that may be clinically useful for their diagnosis.
脑膜瘤是一组具有广泛组织学特征的多样化肿瘤。脑膜瘤有超过12种变体,其基因特征才刚刚开始被描述。血管母细胞型脑膜瘤是世界卫生组织(WHO)分类中的一种脑膜瘤变体,以血管为主。它们并不常见,确定其组织病理学分类可能具有挑战性。由于缺乏定义血管母细胞亚型的生物标志物,且对其肿瘤发生的潜在基因变化了解有限,我们将血管母细胞型脑膜瘤的基因组特征与更常见的脑膜瘤亚型进行了比较。虽然典型的I级脑膜瘤表现为22号染色体单体性或缺乏拷贝数畸变,但14例血管母细胞型脑膜瘤中有13例表现出独特的拷贝数谱——至少一条染色体的多体性,但通常是多条染色体,尤其是5号、13号和20号染色体。具有血管母细胞特征的WHO II级非典型脑膜瘤既有多体性,也有其他非典型脑膜瘤特有的基因畸变。对16例血管母细胞型脑膜瘤中560多个与癌症相关基因的测序表明,这些肿瘤缺乏在其他脑膜瘤变体中发现的常见突变。我们的研究表明,血管母细胞型脑膜瘤具有独特的基因组特征,这可能对其临床诊断有用。