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人类肝母细胞瘤中1号染色体杂合性缺失

Loss of heterozygosity on chromosome 1 in human hepatoblastoma.

作者信息

Kraus J A, Albrecht S, Wiestler O D, von Schweinitz D, Pietsch T

机构信息

Department of Neuropathology, University of Bonn Medical Center, Germany.

出版信息

Int J Cancer. 1996 Aug 7;67(4):467-71. doi: 10.1002/(SICI)1097-0215(19960807)67:4<467::AID-IJC1>3.0.CO;2-Q.

Abstract

In previous studies we have found loss of heterozygosity (LOH) on chromosome arm 11p in 33% of hepatoblastomas (HBs). In addition, cytogenetic studies have revealed aberrations of chromosome arm 1p in single cases. Therefore, we have used the PCR to amplify 10 microsatellites on the short arm and 7 microsatellites on the long arm of chromosome I to assess allelic loss in 32 cases of HB. LOH on chromosome I was found in II cases. Seven HBs showed LOH on chromosome Ip, 7 cases had LOH on Iq, and 3 tumors had LOH on both Ip and Iq. Six HBs with LOH on Ip had LOH at DIS243 (Ip36.3), and one tumor had a loss at DIS80 maintaining heterozygosity at DIS243. A common region of overlap was present at the telomeric chromosomal portion of Ip between DIS80 and DIS243. Of the HBs with LOH on Iq, 4 showed a common region of overlap at Iq3I-q32.I, and the other 3 at DISI609 located more telomerically. The parental origin of the lost allele was of random distribution for chromosome arm Ip and of paternal origin for chromosome arm Iq. Our data suggest that tumor suppressor genes located at the telomeric region of chromosome arm Ip and different regions of chromosome arm Iq may be involved in the pathogenesis of HB.

摘要

在先前的研究中,我们发现33%的肝母细胞瘤(HBs)存在11号染色体短臂杂合性缺失(LOH)。此外,细胞遗传学研究在个别病例中发现了1号染色体短臂的畸变。因此,我们使用聚合酶链反应(PCR)扩增了1号染色体短臂上的10个微卫星和长臂上的7个微卫星,以评估32例HB中的等位基因缺失情况。在11例中发现了1号染色体上的LOH。7例HBs显示1号染色体短臂上有LOH,7例在1号染色体长臂上有LOH,3例肿瘤在1号染色体短臂和长臂上均有LOH。6例1号染色体短臂上有LOH的HBs在DIS243(1p36.3)处有LOH,1例肿瘤在DIS80处有缺失,而在DIS243处保持杂合性。在DIS80和DIS243之间的1号染色体短臂端粒染色体部分存在一个共同的重叠区域。在1号染色体长臂上有LOH的HBs中,4例在1q31-q32.1处显示一个共同的重叠区域,另外3例在更靠近端粒的DIS1609处。缺失等位基因的亲本来源在1号染色体短臂上呈随机分布,而在1号染色体长臂上则为父系来源。我们的数据表明,位于1号染色体短臂端粒区域和1号染色体长臂不同区域的肿瘤抑制基因可能参与了HB的发病机制。

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