Molecular cytogenetic differences between histological subtypes of malignant mesotheliomas:: DNA cytometry and comparative genomic hybridization of 90 cases

Molecular cytogenetic differences between histological subtypes of malignant mesotheliomas:: DNA cytometry and comparative genomic hybridization of 90 cases
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DOI:
10.1002/path.1128
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发表时间:
2002-07-01
影响因子:
7.3
通讯作者:
Johnen, G
Johnen, G
中科院分区:
医学1区
文献类型:
--
作者:
Krismann, M;Müller, KM;Johnen, G

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已确定人类恶性间皮瘤(MM)的亚型与不同的生存时间相关。采用DNA细胞术和比较基因组杂交(CGH)检查了90例MM,重点是主要的组织学亚型:上皮样、肉瘤样和双相型。通过DNA细胞计数的比较显示了中等程度的差异,罕见的中胚层瘤亚组的非整倍体率最高,肉瘤样组的非整倍体率最低。CGH平均每例检出6.2个染色体异常。染色体材料丢失(4.1/例)比获得(2.1/例)更常见。MM没有表现出单一的、特异性的缺陷,但是基因组缺陷的典型模式可以归因于这种肿瘤实体。常见的丢失分别聚集在染色体区域9 p21(34%)、22 q(32%)、4 q31 -32(29%)、4p 12 -13(25%)、14 q12 -24(23%)、1 p21(21%)、13 q13 -14(19%)、3 p21、6 q22、10 p13-pter和17 p12-pter(16%)。常见的增益位于8 q22 -23(18%),1 q23/1 q32(16%),7 p14 -15和15 q22 -25(各14%)。虽然上皮样和肉瘤样MM之间缺陷频率的差异不像多形性中胚层瘤那样明显,但几个染色体位置(3 p,7 q,15 q,17 p)显示出显著的变化。肉瘤样MM最明显的区别特征是扩增子数量高出四倍以上。这些数据表明,MM具有独特的肿瘤生物学特性,具有广泛的异质性,这反映在形态学上,更微妙的是,还反映在亚型的染色体不平衡模式上。版权所有(C)2002约翰威利父子有限公司
It is established that subtypes of human malignant mesotheliomas (MM) are associated with different survival times. Ninety cases of MM were examined using DNA cytometry and comparative genomic hybridization (CGH), with emphasis on the main histological subtypes; epithelioid, sarcomatoid and biphasic. A comparison by DNA cytometry revealed moderate differences, with the rare subgroup of mesodermomas having the highest and the sarcomatoid group the lowest rate of aneuploidy. Using CGH, 6.2 chromosomal imbalances per case on average could be detected. Losses (4.1/case) were more common than gains of chromosomal material (2.1/case). MM show no single, specific defect, but a typical pattern of genomic defects can be attributed to this tumour entity. Common losses are clustered at the chromosomal regions 9p21 (34%), 22q (32%), 4q31-32 (29%), 4p12-13 (25%), 14q12-24 (23%), 1p21 (21%), 13q13-14 (19%), 3p21, 6q22, 10p13-pter and 17p12-pter (16%) each. Common gains are located on 8q22-23 (18%), 1q23/1q32 (16%), 7p14-15 and 15q22-25 (14% each). While differences in the frequencies of the defects between epithelioid and sarcomatoid MM are not as pronounced as are seen with the pleomorphic mesodermomas, several chromosomal locations (3p, 7q, 15q, 17p) show significant variations. The most pronounced distinguishing feature of sarcomatoid MM is a more than fourfold higher number of amplicons. These data indicate that MM has a distinctive tumour biology with a broad spectrum of heterogeneity, as reflected in morphology and also, more subtly, in the patterns of chromosomal imbalances of the subtypes. Copyright (C) 2002 John Wiley Sons, Ltd.