Matrix-comparative genomic hybridization from multicenter formalin-fixed paraffin-embedded colorectal cancer tissue blocks

Matrix-comparative genomic hybridization from multicenter formalin-fixed paraffin-embedded colorectal cancer tissue blocks
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DOI:
10.1186/1471-2407-7-58
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发表时间:
2007-04-02
期刊:
影响因子:
3.8
通讯作者:
Gress, Thomas M.
Gress, Thomas M.
中科院分区:
医学2区
文献类型:
--
作者:
Fensterer, Heiko;Radlwimmer, Bernhard;Gress, Thomas M.

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背景资料:为了确定结直肠癌的基因组特征以进行危险分层,需要对大量癌症患者进行研究并进行广泛的临床随访。多中心的临床研究代表了一个理想的来源,有据可查的存档材料,这种类型的analysis.Methods:为了验证这种材料在技术上是否适合进行矩阵CGH,我们进行了一项试点研究,使用macrosuttered 29福尔马林固定,石蜡包埋的组织样本收集的框架内的EORTC-GI/PETACC-2试验结直肠癌。科学的目的是确定预后的基因组签名区分局部限制(UICC阶段II-III)从系统性晚期(UICC阶段IV)结直肠tumors.Results:大多数存档的组织样本收集在不同的中心是适合执行矩阵CGH。5/7的晚期肿瘤表现为13 q增加和18 q丢失。在局部限制性肿瘤中,只有6/12的肿瘤显示13 q增加,7/12的肿瘤显示18 q减少。间期荧光原位杂交和高分辨率阵列映射的增益13 q证实了阵列数据的有效性,缩小了染色体间隔含有潜在的癌基因。结论:档案,石蜡包埋的组织样本收集在多中心临床试验是适合矩阵CGH分析,并允许识别的预后签名和畸变窝藏潜在的新癌基因。
Background: The identification of genomic signatures of colorectal cancer for risk stratification requires the study of large series of cancer patients with an extensive clinical follow-up. Multicentric clinical studies represent an ideal source of well documented archived material for this type of analyses.Methods: To verify if this material is technically suitable to perform matrix-CGH, we performed a pilot study using macrodissected 29 formalin-fixed, paraffin-embedded tissue samples collected within the framework of the EORTC-GI/PETACC-2 trial for colorectal cancer. The scientific aim was to identify prognostic genomic signatures differentiating locally restricted (UICC stages II-III) from systemically advanced (UICC stage IV) colorectal tumours.Results: The majority of archived tissue samples collected in the different centers was suitable to perform matrix-CGH. 5/7 advanced tumours displayed 13q-gain and 18q-loss. In locally restricted tumours, only 6/12 tumours showed a gain on 13q and 7/12 tumours showed a loss on 18q. Interphase-FISH and high-resolution array-mapping of the gain on 13q confirmed the validity of the array-data and narrowed the chromosomal interval containing potential oncogenes.Conclusion: Archival, paraffin-embedded tissue samples collected in multicentric clinical trials are suitable for matrix-CGH analyses and allow the identification of prognostic signatures and aberrations harbouring potential new oncogenes.