Comparison of DNA copy number changes in malignant mesothelioma, adenocarcinoma and large-cell anaplastic carcinoma of the lung.

Comparison of DNA copy number changes in malignant mesothelioma, adenocarcinoma and large-cell anaplastic carcinoma of the lung.
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DOI:
10.1038/bjc.1998.42
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发表时间:
1998
影响因子:
8.8
通讯作者:
Knuutila, S
Knuutila, S
中科院分区:
医学1区
文献类型:
--
作者:
Bjorkqvist, A M;Tammilehto, L;Nordling, S;Nurminen, M;Anttila, S;Mattson, K;Knuutila, S

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间皮瘤、原发性腺癌和胸膜转移瘤的鉴别诊断常常引起问题。我们对34例恶性间皮瘤和30例原发性肺癌(腺癌,包括支气管肺泡癌和大细胞间变性癌)使用比较基因组杂交(CGH)技术来比较它们的拷贝数变化,并评估CGH在区分这两种类型肿瘤中的应用。在间皮瘤中,遗传物质的获得与丢失发生的频率相同,而在癌症中,遗传物质的获得多于丢失。在间皮瘤中,最常见的变化是4q、6q和14q的缺失以及15q和7p的增加,而在癌症中,8q、1q、7p、5p和6p的增加是最常见的变化。在两种腺癌中通过Southern blot检测到KRAS2扩增。在相同的肿瘤中,CGH显示12p的增加。两种肿瘤在染色体X、1、2p、4、8q、10q、12p、14q、15q、18q上的差异有统计学意义。当使用判别分析比较间皮瘤和肺癌的得失频率时,CGH区分间皮瘤和肺癌的敏感性为81%,特异性为77%。两种肿瘤之间DNA拷贝数变化的差异表明它们是遗传上不同的肿瘤实体。虽然CGH不能作为明确的鉴别方法,但我们能够在大部分异常病例中区分间皮瘤和肺癌。
The differential diagnosis of mesothelioma, primary adenocarcinomas and pleural metastases frequently causes problems. We have used the comparative genomic hybridization (CGH) technique on 34 malignant mesotheliomas and 30 primary lung carcinomas (adenocarcinoma, including bronchoalveolar carcinoma and large-cell anaplastic carcinoma) to compare their copy number changes and to evaluate the use of CGH to distinguish between these two types of tumour. In mesothelioma, gains of genetic material occurred as frequently as losses, whereas gains predominated over losses in carcinoma. In mesothelioma, the most frequent changes were losses in 4q, 6q and 14q and gains in 15q and 7p, whereas gains in 8q, 1q, 7p, 5p and 6p were the most common changes in carcinoma. Amplification of KRAS2 was detected in two adenocarcinomas by Southern blot analysis. CGH showed gains in 12p in the same tumours. Statistically significant differences between the two types of tumour were detected in chromosomes X, 1, 2p, 4, 8q, 10q, 12p, 14q, 15q and 18q. When comparing the frequency of gains and losses between mesothelioma and lung carcinoma using discriminant analysis, the sensitivity of CGH to differentiate mesotheliomas from lung carcinomas was 81% and the specificity 77%. The differences in DNA copy number changes between the two types of tumour suggest that they are genetically different tumour entities. Although CGH cannot be used as a definitive discriminatory method, we were able to distinguish between mesothelioma and lung carcinoma in a large proportion of the abnormal cases.