von Deimling A, Louis D N, von Ammon K, Petersen I, Wiestler O D, Seizinger B R
Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, Charlestown 02129.
Cancer Res. 1992 Aug 1;52(15):4277-9.
Previous studies have shown frequent allelic losses of chromosomes 9p, 10, 17p, and 22q in glial tumors. Other researchers have briefly reported that glial tumors may also show allelic losses of chromosome 19, suggesting a putative tumor suppressor gene locus on this chromosome (D. T. Ransom et al., Proc. Am. Assoc. Cancer Res., 32:302, 1991). To evaluate whether loss of chromosome 19 alleles is common in glial tumors of different types and grades, we performed Southern blot restriction fragment length polymorphism analysis for multiple chromosome 19 loci in 122 gliomas from 116 patients. Twenty-nine tumors had loss of constitutional heterozygosity of 19q, and four tumors had partial deletions of 19q. Allelic losses on 19q were restricted to grade III anaplastic astrocytomas (4/9) and grade IV glioblastomas (11/46), grade II oligodendrogliomas (2/5) and grade III anaplastic oligodendrogliomas (2/2), and grade II (5/8) and grade III (5/7) mixed oligoastrocytomas. These data demonstrate genetic similarities between astrocytomas, oligodendrogliomas, and mixed glial tumors and indicate the presence of a glial tumor suppressor gene on chromosome 19q.
以往研究表明,胶质肿瘤中常出现9号染色体短臂、10号、17号染色体短臂和22号染色体长臂的等位基因缺失。其他研究人员曾简要报道,胶质肿瘤也可能出现19号染色体的等位基因缺失,提示该染色体上存在一个假定的肿瘤抑制基因位点(D.T.兰塞姆等人,《美国癌症研究协会会刊》,第32卷:302页,1991年)。为评估19号染色体等位基因缺失在不同类型和级别的胶质肿瘤中是否常见,我们对116例患者的122个胶质瘤的多个19号染色体位点进行了Southern印迹限制性片段长度多态性分析。29个肿瘤出现19号染色体长臂的结构杂合性缺失,4个肿瘤出现19号染色体长臂的部分缺失。19号染色体长臂上的等位基因缺失仅限于III级间变性星形细胞瘤(4/9)和IV级胶质母细胞瘤(11/46)、II级少突胶质细胞瘤(2/5)和III级间变性少突胶质细胞瘤(2/2),以及II级(5/8)和III级(5/7)混合性少突星形细胞瘤。这些数据证明了星形细胞瘤、少突胶质细胞瘤和混合性胶质肿瘤之间的遗传相似性,并表明19号染色体长臂上存在一个胶质肿瘤抑制基因。