Mollenhauer J, Wiemann S, Scheurlen W, Korn B, Hayashi Y, Wilgenbus K K, von Deimling A, Poustka A
Division of Molecular Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Nat Genet. 1997 Sep;17(1):32-9. doi: 10.1038/ng0997-32.
Loss of sequences from human chromosome 10q has been associated with the progression of human cancer. Medulloblastoma and glioblastoma multiforme are the most common malignant brain tumours in children and adults, respectively. In glioblastoma multiforme, the most aggressive form, 80% of the tumours show loss of 10q. We have used representational difference analysis to identify a homozygous deletion at 10q25.3-26.1 in a medulloblastoma cell line and have cloned a novel gene, DMBT1, spanning this deletion. DMBT1 shows homology to the scavenger receptor cysteine-rich (SRCR) superfamily. Intragenic homozygous deletions has been detected in 2/20 medulloblastomas and in 9/39 glioblastomas multiformes. Lack of DMBT1 expression has been demonstrated in 4/5 brain-tumour cell lines. We suggest that DMBT1 is a putative tumour-suppressor gene implicated in the carcinogenesis of medulloblastoma and glibolastoma multiforme.
人类10号染色体q臂序列的缺失与人类癌症的进展有关。髓母细胞瘤和多形性胶质母细胞瘤分别是儿童和成人中最常见的恶性脑肿瘤。在最具侵袭性的多形性胶质母细胞瘤中,80%的肿瘤显示10q缺失。我们利用代表性差异分析在一个髓母细胞瘤细胞系中鉴定出10q25.3 - 26.1处的纯合缺失,并克隆了一个跨越该缺失区域的新基因DMBT1。DMBT1与富含半胱氨酸的清道夫受体(SRCR)超家族具有同源性。在20例髓母细胞瘤中有2例以及39例多形性胶质母细胞瘤中有9例检测到基因内纯合缺失。在5个脑肿瘤细胞系中有4个证实缺乏DMBT1表达。我们认为DMBT1是一个推定的肿瘤抑制基因,与髓母细胞瘤和多形性胶质母细胞瘤的致癌作用有关。