Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution
Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution
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DOI：
10.1038/nature08489
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发表时间：
2009-10-08
期刊：
影响因子：
64.8
通讯作者：
Aparicio, Samuel
中科院分区：
文献类型：
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作者：
Shah, Sohrab P.;Morin, Ryan D.;Aparicio, Samuel
下一代测序的最新进展（1-4）使得能够精确地表征了在单个癌症发展和进展过程中发生的所有体细胞编码突变。在这里，我们使用了这些方法来对深度触发转移性转移性叶状叶状乳腺癌的基因组（> 43倍）和转录组进行测序。我们发现了32个体内存在的32个体外编码突变，并测量了9年前出现的同一患者的原发性肿瘤中DNA中这些体细胞突变的频率。在9年前诊断时，存在32个突变（在ABCB11，HAUS3，SLC24A4，SNX4和PALB2）中，有5个普遍存在。在较低的频率（1-13％）下，未在原发性肿瘤中检测到19个，两个不确定。基因组和转录组数据的组合分析揭示了两个新的RNA编辑事件，它们回顾了SRP9和COG3的氨基酸序列。综上所述，我们的数据表明，单核苷酸突变异质性可以是低或中级原发性乳腺癌的特性，并且疾病进展可能会发生显着的进化。
Recent advances in next generation sequencing(1-4) have made it possible to precisely characterize all somatic coding mutations that occur during the development and progression of individual cancers. Here we used these approaches to sequence the genomes (>43-fold coverage) and transcriptomes of an oestrogen-receptor-apositive metastatic lobular breast cancer at depth. We found 32 somatic non-synonymous coding mutations present in the metastasis, and measured the frequency of these somatic mutations in DNA from the primary tumour of the same patient, which arose 9 years earlier. Five of the 32 mutations (in ABCB11, HAUS3, SLC24A4, SNX4 and PALB2) were prevalent in the DNA of the primary tumour removed at diagnosis 9 years earlier, six ( in KIF1C, USP28, MYH8, MORC1, KIAA1468 and RNASEH2A) were present at lower frequencies (1-13%), 19 were not detected in the primary tumour, and two were undetermined. The combined analysis of genome and transcriptome data revealed two new RNA-editing events that recode the amino acid sequence of SRP9 and COG3. Taken together, our data show that single nucleotide mutational heterogeneity can be a property of low or intermediate grade primary breast cancers and that significant evolution can occur with disease progression.