Fensterer Heiko, Radlwimmer Bernhard, Sträter Jörn, Buchholz Malte, Aust Daniela E, Julié Catherine, Radvanyi François, Nordlinger Bernard, Belluco Claudio, Van Cutsem Eric, Köhne Claus-Henning, Kestler Hans A, Schwaenen Carsten, Nessling Michelle, Lutz Manfred P, Lichter Peter, Gress Thomas M
Department of Internal Medicine I, University of Ulm, Ulm, Germany.
BMC Cancer. 2007 Apr 2;7:58. doi: 10.1186/1471-2407-7-58.
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.
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.
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.
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.
识别用于风险分层的结直肠癌基因组特征需要对大量癌症患者进行广泛的临床随访研究。多中心临床研究是这类分析中记录良好的存档材料的理想来源。
为验证这种材料在技术上是否适合进行基质比较基因组杂交(matrix-CGH),我们进行了一项初步研究,使用在欧洲癌症研究与治疗组织-胃肠道/欧洲癌症协作组-2(EORTC-GI/PETACC-2)结直肠癌试验框架内收集的29个经宏观解剖的福尔马林固定、石蜡包埋组织样本。科学目的是识别区分局部受限(国际抗癌联盟(UICC)II-III期)和全身进展期(UICC IV期)结直肠癌肿瘤的预后基因组特征。
在不同中心收集的大多数存档组织样本适合进行基质比较基因组杂交。5/7例进展期肿瘤显示13q增益和18q缺失。在局部受限肿瘤中,只有6/12例肿瘤显示13q增益,7/12例肿瘤显示18q缺失。对13q增益进行的间期荧光原位杂交(Interphase-FISH)和高分辨率阵列定位证实了阵列数据的有效性,并缩小了包含潜在致癌基因的染色体区间。
在多中心临床试验中收集的存档石蜡包埋组织样本适合进行基质比较基因组杂交分析,并能够识别预后特征以及含有潜在新致癌基因的畸变。