A genome-wide study of cytogenetic changes in colorectal cancer using SNP microarrays: opportunities for future personalized treatment.
A genome-wide study of cytogenetic changes in colorectal cancer using SNP microarrays: opportunities for future personalized treatment.
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DOI：
10.1371/journal.pone.0031968
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kibriya MG
中科院分区：
文献类型：
--
作者：
Jasmine F;Rahaman R;Dodsworth C;Roy S;Paul R;Raza M;Paul-Brutus R;Kamal M;Ahsan H;Kibriya MG
在结直肠癌（CRC）中，通常使用比较基因组杂交（CGH）阵列研究染色体不稳定性（CIN）。我们使用Illumina的基于Infinium的SNP阵列研究了来自86名CRC患者的成对（肿瘤和周围健康）新鲜冷冻组织。这种方法使我们能够研究CRC中的CIN，同时分析拷贝数（CN）和B等位基因频率（BAF）-等位基因组成的代表。这些数据帮助我们检测单等位基因和双等位基因扩增/缺失、拷贝中性杂合性丢失和混合细胞群体的嵌合体水平，其中一些不能用不测量BAF的其他方法进行评估。我们确定了CN异常与不同CRC表型（组织学诊断、位置、肿瘤分级、分期、MSI和淋巴结转移）之间的相关性。我们显示了在CRC中观察到的CN变化区域与先前在其他实体癌研究中报告的区域之间的共性（例如20 q、13 q、8 q、5 p的扩增和18 q、17 p和8 p的缺失）。从治疗靶点数据库中，我们确定了相关药物，靶向位于CN变化区域的基因，已批准或正在试验用于其他癌症和常见疾病。基于个体化细胞遗传学诊断，这些药物可能被考虑用于未来的CRC治疗试验。我们还发现了许多含有基因的区域，这些区域目前没有被任何相关药物靶向，这些药物可能被考虑用于未来的药物发现研究。我们的研究显示了高密度SNP芯片在CRC细胞遗传学研究中的应用及其在个体化治疗中的潜在效用。
In colorectal cancer (CRC), chromosomal instability (CIN) is typically studied using comparative-genomic hybridization (CGH) arrays. We studied paired (tumor and surrounding healthy) fresh frozen tissue from 86 CRC patients using Illumina's Infinium-based SNP array. This method allowed us to study CIN in CRC, with simultaneous analysis of copy number (CN) and B-allele frequency (BAF) - a representation of allelic composition. These data helped us to detect mono-allelic and bi-allelic amplifications/deletion, copy neutral loss of heterozygosity, and levels of mosaicism for mixed cell populations, some of which can not be assessed with other methods that do not measure BAF. We identified associations between CN abnormalities and different CRC phenotypes (histological diagnosis, location, tumor grade, stage, MSI and presence of lymph node metastasis). We showed commonalities between regions of CN change observed in CRC and the regions reported in previous studies of other solid cancers (e.g. amplifications of 20q, 13q, 8q, 5p and deletions of 18q, 17p and 8p). From Therapeutic Target Database, we identified relevant drugs, targeted to the genes located in these regions with CN changes, approved or in trials for other cancers and common diseases. These drugs may be considered for future therapeutic trials in CRC, based on personalized cytogenetic diagnosis. We also found many regions, harboring genes, which are not currently targeted by any relevant drugs that may be considered for future drug discovery studies. Our study shows the application of high density SNP arrays for cytogenetic study in CRC and its potential utility for personalized treatment.
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影响因子：
37.3
作者：
Berg M;Agesen TH;Thiis-Evensen E;INFAC-study group;Merok MA;Teixeira MR;Vatn MH;Nesbakken A;Skotheim RI;Lothe RA
通讯作者：
Lothe RA
影响因子：
6.4
作者：
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通讯作者：
Yamagishi, H
影响因子：
4.7
作者：
Andersen, Claus Lindbjerg;Wiuf, Carsten;Orntoft, Torben Falck
通讯作者：
Orntoft, Torben Falck
影响因子：
4.7
作者：
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通讯作者：
van Engeland, Manon
影响因子：
3.4
作者：
Ahmed, S;Banerjea, A;Dorudi, S
通讯作者：
Dorudi, S