Marked intratumoral heterogeneity of c-myc and CyclinD1 but not of c-erbB2 amplification in breast cancer
Marked intratumoral heterogeneity of c-myc and CyclinD1 but not of c-erbB2 amplification in breast cancer
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DOI：
10.1097/01.lab.0000032371.16521.40
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发表时间：
2002-10-01
影响因子：
5
通讯作者：
Kreipe, H
中科院分区：
文献类型：
--
作者：
Glöckner, S;Buurman, H;Kreipe, H
肿瘤内异质性反映了亚克隆多样性，并可能影响治疗反应。为了研究原发性乳腺癌标本的分子异质性，我们在宏观和微观上分别测定了生长调节基因（c-erbB 2、拓扑异构酶II α、c-myc和cyclinD 1）的扩增状态。单个肿瘤的面积（n = 21）。使用激光辅助显微切割和定量PCR，我们发现了显着的瘤内异质性与不同的模式，为每个基因。扩增模式的分子异质性可以在宏观（0.5至几厘米）和微观（10至几百微米）远处肿瘤区域之间证明。C-erbB 2扩增被证明是个体肿瘤中最稳定的扩增，只有36%的扩增病例发生异质性。相比之下，c-myc和cyclinD 1的扩增在绝大多数扩增病例中显示不同的模式（100%和83%）。c-erbB 2扩增的恒定性强调了其在乳腺癌生物学中的假定重要性。我们的结论是，乳腺癌的分子异质性，在这项研究中证明，需要彻底的和代表性的采样时，考虑到体细胞突变的生物学意义的不同的肿瘤区域。异质性模式可用于追踪单个肿瘤的不同区室内的克隆进化。
Intratumoral heterogeneity mirrors subclonal diversity and might affect treatment response. To investigate molecular heterogeneity of primary breast cancer specimens, we determined the amplification status of growth regulatory genes (c-erbB2, topoisomerase IIalpha, c-myc, and cyclinD1) in macroscopically and microscopically separate. areas of individual tumors (n = 21). Using laser-assisted microdissection and quantitative PCR, we found marked intratumoral heterogeneity with different patterns for each gene. Molecular heterogeneity in amplification pattern could be demonstrated between both macroscopically (0.5 to several centimeters) and microscopically (10 to several hundred micrometers) distant tumor areas. C-erbB2 amplification proved to be the most stable amplification in individual tumors, with heterogeneity occurring in only 36% of amplified cases. By contrast, amplification of c-myc and cyclinD1 revealed varying patterns in the vast majority of amplified cases (100% and 83%). The constancy of c-erbB2 amplification underlines its presumed importance in breast cancer biology. We conclude that the molecular heterogeneity of breast cancer as evidenced in this study requires thorough and representative sampling of different tumor areas when the biologic significance of somatic mutations is considered. Patterns of heterogeneity can be used to trace the clonal evolution within different compartments of an individual tumor.