Molecular cytogenetic analysis of non-small cell lung carcinoma by spectral karyotyping and comparative genomic hybridization

Molecular cytogenetic analysis of non-small cell lung carcinoma by spectral karyotyping and comparative genomic hybridization
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DOI:
10.1016/s0165-4608(00)00363-0
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发表时间:
2001-03-01
影响因子:
--
通讯作者:
Squire, JA
Squire, JA
中科院分区:
其他
文献类型:
--
作者:
Luk, C;Tsao, MS;Squire, JA

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通过对NSCLC各主要组织亚型的两个细胞系,即鳞状细胞癌(SQCC)和腺癌(ADC)的光谱核型(SKY)分析发现,染色体重排的总体模式比比较基因组杂交(CGH)或G显带分析所存在或预测的程度更大。为了研究这些观察结果,我们用CGH对8个原发肿瘤和15个细胞系的DNA进行了筛选。结果表明,获得染色体臂最多的是5p(70%)、Sq(65%)、15q(52%)、20q(48%)、IQ(43%)、19q(39%)、3q(35%)和11q(35%)。染色体缺失的发生率较低,包括18q(39%)、9(35%)、6q(30%)、13q(21%)、5q12-q32(17%)和19p(17%)。扩增产物分别位于2p23-p24、3q24-q27、5p、6cen-p21.1、6q26、7p21、7q31、8q、11q13-qTER、20q12-q13.2。比较两种主要组织学亚型的CGH发现,ADC在1q22-q32.2、15q、20q的增益和6q、13q和18q的损失是常见的,而SQCC在3q表现为增益/扩增。在这两种类型的肿瘤中,65%的肿瘤通过CGH获得了远端8q。直接荧光原位杂交(FISH)分析证实有低水平的MYCC扩增。结合分子细胞遗传学分析方法检测到的全部染色体改变的模式表明,在非小细胞肺癌中更容易检测到反复出现的亚型依赖的异常。(C)2001爱思唯尔科学公司。保留所有权利。
The overall pattern of chromosomal changes detected by spectral karyotype (SKY) analysis of two cell lines of each major histological subtype of NSCLC, namely squamous cell carcinoma (SQCC) and adenocarcinoma (ADC), indicated a greater degree of chromosomal rearrangement, than was present or predicted by either comparative genomic hybridization (CGH) or G-banding analysis alone. To investigate these observations, CGH was used to screen DNA derived from 8 primary tumors and 15 cell lines. The results indicated that the most frequently gained chromosome arms were 5p (70%), Sq (65%), 15q (52%), 20q (48%), Iq (43%)? 19q (39%), 3q (35%), and 11q (35%). Chromosomal losses were less frequently observed, and included 18q (39%), 9 (35 %), 6q (30%)? 13q (21%), 5q12-q32 (17%), and 19p (17%). Amplifications were found on 2p23-p24, 3q24-q27, 5p, 6cen-p21.1, 6q26, 7p21, 7q31, 8q, 11q13-qter, 20q12-q13.2. Comparison between CGH findings of the two major histological subtypes showed that gains at 1q22-q32.2, 15q, 20q, and losses at 6q, 13q, and 18q was common in ADCs, whereas SQCCs exhibited gains/amplifications at 3q. Distal 8q was gained by CGH in 65% of tumors of both subtypes. Low level MYCC amplification was confirmed by direct fluorescence in situ hybridization (FISH) analysis. The pattern of overall chromosomal changes detected using combinations of molecular cytogenetic analytical methods suggests that it will be easier to detect recurrent subtype-dependent aberrations in NSCLC. (C) 2001 Elsevier Science, Inc. All rights reserved.