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首页> 外文期刊>Cellular Oncology: Analytical Cellular Pathology >Intratumor Genetic Heterogeneity of Breast Carcinomas as Determined by Fine Needle Aspiration and TaqMan Low Density Array
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Intratumor Genetic Heterogeneity of Breast Carcinomas as Determined by Fine Needle Aspiration and TaqMan Low Density Array

机译：细针穿刺和TaqMan低密度阵列确定的乳腺癌肿瘤内遗传异质性

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Background: Gene expression profiling is thought to be an important tool in determining treatment strategies for breast cancer patients. Tissues for such analysis may at a preoperative stage be obtained, by fine needle aspiration (FNA) allowing initiation of neoadjuvant treatment. To evaluate the extent of the genetic heterogeneity within primary breast carcinomas, we examined whether a gene expression profile obtained by FNA was representative of the tumor.Methods: Tumors from 12 consecutive cases of early predominantly estrogen receptor positive (ER+) breast cancer patients undergoing primary surgery were split in halves and FNAs were obtained from each half. A tissue biopsy of the tumors was also snap-frozen for comparison. Non-amplified RNA was investigated by the novel qRT-PCR-based technique, Low Density Array (LDA) using 4 reference genes and 44 target genes.Results: Comparison of gene expression at the single gene level in the two FNA samples from each tumor demonstrated various degrees of heterogeneity. However, compared as gene expression profiles, intratumor correlations for 9/12 patients were high and these pairs could in a theoretical blinding of all the FNAs be correctly matched by statistical analysis. High correlations between the gene profiles of tumor FNAs and tissue biopsies from the same patient were observed for all patients. A cluster analysis identified clustering of both the two FNAs and the tissue biopsy of the same 9 patients.Conclusion: The overall genetic heterogeneity of breast carcinomas, as sampled by FNA, does not prohibit generation of useful gene profiles for treatment decision making. However, sampling and analysis strategies should take heterogeneity within a tumor, and varying heterogeneity amongst the single genes, into account.
机译：背景：基因表达谱分析被认为是确定乳腺癌患者治疗策略的重要工具。可以在术前通过细针抽吸术（FNA）获得新辅助治疗的组织，以便进行此类分析。为了评估原发性乳腺癌中遗传异质性的程度，我们检查了通过FNA获得的基因表达谱是否可以代表该肿瘤。方法：连续12例早期主要为雌激素受体阳性（ER +）乳腺癌患者的肿瘤将手术分为两半，从每半部分获得FNA。还对肿瘤的组织活检进行了速冻以进行比较。通过基于qRT-PCR的新型技术低密度阵列（LDA），使用4个参考基因和44个靶基因对未扩增的RNA进行了研究。结果：比较每个肿瘤的两个FNA样品中单个基因水平的基因表达表现出不同程度的异质性。然而，与基因表达谱相比，9/12患者的肿瘤内相关性很高，并且这些对在理论上可以通过统计分析正确匹配所有FNA。对于所有患者，均观察到肿瘤FNA的基因谱与同一患者的组织活检之间的高度相关性。聚类分析确定了两个FNA的聚类以及同一9例患者的组织活检。结论：FNA采样显示，乳腺癌的总体遗传异质性并不妨碍生成有用的基因谱以用于治疗决策。但是，采样和分析策略应考虑肿瘤内的异质性，并考虑单个基因之间的异质性。

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