本期封面背景图片所示为来自这项研究中所用原发小叶肿瘤的组织。
下一代测序方法被用来研究来自一个患者（而不是来自一个细胞系或异种移植物）的一种“雌激素-受体-阿尔法-阳性”转移性小叶乳腺癌的基因组和转录组，研究的时段是从原发肿瘤被诊断出到出现转移之间的9年时间。
对同一患者转移肿瘤和原发肿瘤中的体细胞非同义编码突变所做比较，以及对基因组和转录组数据的组合分析，加深了我们对会随病情发展出现的突变演化的认识。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 461, 809-813 (8 October 2009) | doi:10.1038/nature08489
Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution
Sohrab P. Shah1,2,8, Ryan D. Morin3,8, Jaswinder Khattra1, Leah Prentice1, Trevor Pugh3, Angela Burleigh1, Allen Delaney3, Karen Gelmon4, Ryan Guliany1, Janine Senz2, Christian Steidl2,5, Robert A. Holt3, Steven Jones3, Mark Sun1, Gillian Leung1, Richard Moore3, Tesa Severson3, Greg A. Taylor3, Andrew E. Teschendorff6, Kane Tse1, Gulisa Turashvili1, Richard Varhol3, René L. Warren3, Peter Watson7, Yongjun Zhao3, Carlos Caldas6, David Huntsman2,5, Martin Hirst3, Marco A. Marra3 & Samuel Aparicio1,2,5
1 Molecular Oncology,
2 Centre for Translational and Applied Genomics,
3 Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
4 Medical Oncology, BC Cancer Agency, 600 West 10th Avenue, Vancouver V5Z 1L3, Canada
5 Department of Pathology, University of British Columbia, G227-2211 Wesbrook Mall, British Columbia, Vancouver V6T 2B5, Canada
6 Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
7 Deeley Research Centre, BC Cancer Agency, Victoria V8R 6V5, Canada
8 These authors contributed equally to this work.
Correspondence to: Marco A. Marra3Samuel Aparicio1,2,5 Correspondence and requests for materials should be addressed to M.A.M. or S.A.
Recent advances in next generation sequencing1, 2, 3, 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--positive 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.
