Loss of heterozygosity in the retinoblastoma tumor suppressor gene in skull base chordomas and chondrosarcomas
Loss of heterozygosity in the retinoblastoma tumor suppressor gene in skull base chordomas and chondrosarcomas
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DOI：
10.1016/s0090-3019(96)00432-6
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发表时间：
1997-02-01
影响因子：
--
通讯作者：
Wolfe, D
中科院分区：
文献类型：
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作者：
Eisenberg, MB;Woloschak, M;Wolfe, D
视网膜母细胞瘤（Rb）基因是一种具有良好特征的肿瘤抑制基因，其杂合性缺失与许多恶性肿瘤包括骨肉瘤和乳腺癌有关。脊索瘤和软骨肉瘤是一种罕见的颅底肿瘤，有局部复发的倾向，对常规放疗有抵抗力，转移率为5%-30%。除了所谓的“软骨样脊索瘤”外，组织学特征与这些肿瘤的临床行为或生长模式无关。迄今为止还没有研究调查肿瘤抑制基因或癌基因在这些罕见肿瘤的发展和持续生长中所起的作用。方法为了评估视网膜母细胞瘤肿瘤抑制基因在脊索瘤和软骨肉瘤中的作用，我们筛选了位于颅底的7例脊索瘤和2例软骨肉瘤Rb基因杂合性缺失（LOH）。从肿瘤标本和匹配的对照组织中提取基因组DNA，利用聚合酶链反应技术，从每个标本中扩增内含子17和20。内含子17产物用限制性内切酶酶切，1%琼脂糖凝胶电泳。内含子20扩增产物在不变性的6%聚丙烯酰胺凝胶上电泳。结果我们在2/7脊索瘤和0/2软骨肉瘤中证实了视网膜母细胞瘤基因内含子17的LOH。具有LOH的两个脊索瘤是特别具有侵袭性的肿瘤，表现为广泛累及颅底，在根治性切除后迅速复发。结论Rb基因的改变可能在颅底脊索瘤的生长中起作用，Rb基因的缺失可以作为肿瘤侵袭性更强的标志。本报告是首次评估Rb基因在脊索瘤或软骨肉瘤中的作用，也是首次报道Rb基因等位基因缺失在颅底脊索瘤中的作用。(C) 1997年由爱思唯尔科学公司
BACKGROUND The retinoblastoma (Rb) gene is a well characterized tumor suppressor gene in which loss of heterozygosity has been implicated in a number of malignancies including osteosarcoma and breast carcinoma. Chordomas and chondrosarcomas are rare skull base neoplasms with a propensity for local recurrences, resistance to conventional radiotherapy, and a 5%-30% incidence of metastases. Except for the so called ''chondroid chordoma,'' histologic features do not correlate with the clinical behavior or growth patterns of these tumors. No study to date has investigated what role tumor suppressor genes or oncogenes play in the development and continued growth of these rare neoplasms.METHODS In order to evaluate the role of the retinoblastoma tumor suppressor gene in chordomas and chondrosarcomas we screened seven chordomas and two chondrosarcomas located at the skull base for loss of heterozygosity (LOH) of the Rb gene. Genomic DNA was extracted from tumor specimens as well as matched control tissue and utilizing a polymerase chain reaction technique, intron 17 and 20 were amplified from each specimen. The intron 17 product was then digested with the restriction endonuclease X bal followed by electrophoresis on a 1% agrose gel. The intron 20 amplified products were electrophoresed on a nondenaturing 6% polyacrylamide gel,RESULTS We demonstrated LOH at intron 17 of the retinoblastoma gene in 2/7 chordomas and in 0/2 chondrosarcomas. The two chordomas possessing LOH were particularly aggressive tumors demonstrating extensive involvement of the skull base and rapid recurrences following radical resections.CONCLUSIONS Alterations of the Rb gene may play a role in the growth of skull base chordomas with LOH of the Rb gene serving as a marker for more aggressive tumors, This report represents the first study evaluating the Rb gene in chordomas or chondrosarcomas and is the first report of allelic loss of the Rb gene in skull base chordomas. (C) 1997 by Elsevier Science Inc.