杂合性缺失揭示了成血管细胞瘤在22q13处存在非VHL等位基因缺失。

Loss of heterozygosity reveals non-VHL allelic loss in hemangioblastomas at 22q13.

作者信息

Beckner Marie E, Sasatomi Eizaburo, Swalsky Patricia A, Hamilton Ronald L, Pollack Ian F, Finkelstein Sydney D

机构信息

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

出版信息

Hum Pathol. 2004 Sep;35(9):1105-11. doi: 10.1016/j.humpath.2004.05.014.

DOI:10.1016/j.humpath.2004.05.014

PMID:15343513

Abstract

Hemangioblastomas (HBs) are low-grade (World Health Organization grade I/IV) central nervous system (CNS) tumors that frequently contain VHL (3p26) mutations. They occur sporadically and in von Hippel Lindau (VHL) disease. Encoded pVHL aids degradation of hypoxia-inducible factors (HIFs) in the presence of normal oxygen levels. HBs provide an in vivo view of HIF effects within a CNS tumor. Typically, HBs are cystic tumors containing a mural nodule formed by noninvasive, vacuolated stromal cells that are embedded in a network of capillaries. Nine HBs, consecutively resected from 8 patients at our institution during a recent 2-year time span, were evaluated for additional losses of tumor suppressor genes. Non-VHL microsatellites studied for loss of heterozygosity (LOH) are near tumor suppressor genes lost in gliomas, pituitary adenomas, several CNS tumors on 22q, neurofibromatosis 1, and colon carcinomas (13, 2, 2, 1, and 2 markers for each, respectively). LOH in the region of 3p21.3-3p26.3 occurred in 3 of 8 HBs informative for at least 1 marker (D3S1539, D3S2303, or D3S2373). By using 2 markers (D22S417 and D22S532) for 22q13.2, LOH was found in 5 of 8 informative HBs. All 3 HBs with allelic losses near VHL also showed LOH at 22q13.2. No consistent losses were found with markers for 1p34, LMYC, 5q21, 5q32, 9p21, 10q23, 17p13, and 19q13. LOH for the 22q13.2 region in HBs suggests that the loss of another tumor suppressor gene is involved in the pathogenesis of HBs in addition to VHL. Absence of LOH for glioma markers is consistent with the low-grade behavior of HBs.

摘要

血管母细胞瘤（HBs）是低级别（世界卫生组织I/IV级）中枢神经系统（CNS）肿瘤，常伴有VHL（3p26）突变。它们可散发性发生，也见于冯·希佩尔-林道（VHL）病。在正常氧水平存在时，编码的pVHL有助于缺氧诱导因子（HIFs）的降解。HBs为CNS肿瘤内HIF效应提供了体内观察视角。通常，HBs是囊性肿瘤，含有由非侵袭性、空泡化的基质细胞形成的壁结节，这些细胞嵌入毛细血管网络中。在最近2年时间里，从我们机构的8名患者中连续切除了9个HBs，评估其肿瘤抑制基因的额外缺失情况。针对杂合性缺失（LOH）研究的非VHL微卫星靠近在胶质瘤、垂体腺瘤、22q上的几种CNS肿瘤、神经纤维瘤病1型和结肠癌中缺失的肿瘤抑制基因（分别针对每个基因有13、2、2、1和2个标记）。在至少1个标记（D3S1539、D3S2303或D3S2373）信息充足的8个HBs中，有3个在3p21.3 - 3p26.3区域出现LOH。通过使用针对22q13.2的2个标记（D22S417和D22S532），在8个信息充足的HBs中有5个发现了LOH。所有在VHL附近存在等位基因缺失的3个HBs在22q13.2处也显示出LOH。对于1p34、LMYC、5q21、5q32、9p21、10q23、17p13和19q13的标记，未发现一致的缺失情况。HBs中22q13.2区域的LOH表明，除VHL外，另一个肿瘤抑制基因的缺失也参与了HBs的发病机制。胶质瘤标记未出现LOH与HBs的低级别行为一致。