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首页> 外文期刊>Nature Communications >DNA copy number changes define spatial patterns of heterogeneity in colorectal cancer
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DNA copy number changes define spatial patterns of heterogeneity in colorectal cancer

机译：DNA拷贝数变化定义了大肠癌异质性的空间格局

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Genetic heterogeneity between and within tumours is a major factor determining cancer progression and therapy response. Here we examined DNA sequence and DNA copy-number heterogeneity in colorectal cancer (CRC) by targeted high-depth sequencing of 100 most frequently altered genes. In 97 samples, with primary tumours and matched metastases from 27 patients, we observe inter-tumour concordance for coding mutations; in contrast, gene copy numbers are highly discordant between primary tumours and metastases as validated by fluorescent in situ hybridization. To further investigate intra-tumour heterogeneity, we dissected a single tumour into 68 spatially defined samples and sequenced them separately. We identify evenly distributed coding mutations in APC and TP5 3 in all tumour areas, yet highly variable gene copy numbers in numerous genes. 3D morpho-molecular reconstruction reveals two clusters with divergent copy number aberrations along the proximal–distal axis indicating that DNA copy number variations are a major source of tumour heterogeneity in CRC.
机译：肿瘤之间和肿瘤内部的遗传异质性是决定癌症进展和治疗反应的主要因素。在这里，我们通过针对性地对100个最频繁改变的基因进行了深度测序，检查了大肠癌（CRC）中的DNA序列和DNA拷贝数异质性。在97个样本中，有来自27例患者的原发性肿瘤和匹配的转移灶，我们观察到了编码突变的肿瘤间一致性。相反，通过荧光原位杂交验证，原发肿瘤和转移之间的基因拷贝数高度不一致。为了进一步研究肿瘤内异质性，我们将单个肿瘤解剖为68个空间定义的样品，并分别对其进行测序。我们确定在所有肿瘤区域中APC和TP5 3中均匀分布的编码突变，但在众多基因中的基因拷贝数却高度可变。 3D形态分子重建揭示了两个簇，它们沿近端-远端轴具有不同的拷贝数畸变，表明DNA拷贝数变异是CRC肿瘤异质性的主要来源。

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