Topographical distributions of allelic loss in individual non-small-cell lung cancers
Topographical distributions of allelic loss in individual non-small-cell lung cancers
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DOI：
10.1016/s0002-9440(10)64611-1
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发表时间：
2000-09-01
影响因子：
6
通讯作者：
Takahashi, T
中科院分区：
文献类型：
--
作者：
Yatabe, Y;Konishi, H;Takahashi, T
非小细胞肺癌，尤其是腺癌，具有高度的形态异质性，因为其发生是一个多步骤的过程，涉及多个基因改变的顺序累积，形态异质性可能代表了单个肿瘤内基因改变的横断面观。因此，我们研究了10例非小细胞肺癌中杂合性缺失(LOH)事件的地形分布，以调查是否以及哪些基因改变与形态进展有关。在10例信息性病例中，分别有6例、8例和6例检测到TP53、17p13.3和3p基因座的杂合性缺失。在每个病例中，尽管形态不同，但肿瘤的所有部分都具有一致的杂合性缺失。相反，已报道与肿瘤晚期相关的2q、9p和22q的杂合性缺失在3例中的2例、8例中的4例和1例的LOH中的分布是不同的。在这些病例中，LOH的存在主要与肿瘤的形态分级有关。这些发现表明，即使在个别肿瘤中也能看到特定基因座上基因变化的累积特征。此外，本研究还表明，对单个肿瘤的横断面检查对于更好地了解肺癌的分子发病机制也很重要。
Non-small-cell carcinomas of the lung, especially adenocarcinomas, are characterized by a high degree of morphological heterogeneity, As carcinogenesis has been suggested to be a multistep process involving sequential accumulation of multiple genetic alterations, morphological heterogeneity may represent a cross-sectional view of genetic alterations within individual tumors. We therefore examined the topographical distribution of loss of heterozygosity (LOH) events within 10 non-small-cell lung cancers to investigate whether, and which, genetic alterations are accumulated in relation to morphological progression. LOH at the TP53, 17p13.3, and 3p loci was detected in six, eight, and six of 10 informative cases, respectively. In each case, all portions of the tumor shared concordant LOH despite morphological diversity. In contrast, distributions of LOH at 2q, 9p, and 22q, which have been reported to be associated with the advanced stages of tumors, were divergent in two of three, four of eight, and one of one cases with LOH, respectively. In these cases, presence of LOH was mostly related to the morphological tumor grades. These findings suggest the accumulative feature of genetic alterations in particular loci that can be seen even in individual tumors. Furthermore, the present study indicated that cross-sectional examination of individual tumors is also important for better understanding of molecular pathogenesis of lung cancers.