随着最新DNA测序技术的问世，现在有可能对整个一个基因组进行筛选，以寻找与肿瘤进展相关的基因变化。
这种方法已被用来获取来自一位44岁非洲裔美国人乳腺癌患者（其所患为Basal-型乳腺癌）的四个DNA样本的完整序列， 这四个DNA样本分别是：原发性肿瘤、周围血液、一个脑转移样本和一个来自原发性肿瘤的“first-passage”异种移植。
突变分析表明，转移肿瘤特定选择来自原发性肿瘤的、含有业已存在突变的一个亚类的细胞，并且还会形成少量新突变。(生物谷Bioon.com)
生物谷推荐原文出处：
Nature doi:10.1038/nature08989
Genome remodelling in a basal-like breast cancer metastasis and xenograft
Li Ding1,2,10, Matthew J. Ellis3,4,10, Shunqiang Li3, David E. Larson1, Ken Chen1, John W. Wallis1,2, Christopher C. Harris1, Michael D. McLellan1, Robert S. Fulton1,2, Lucinda L. Fulton1,2, Rachel M. Abbott1, Jeremy Hoog3, David J. Dooling1,2, Daniel C. Koboldt1, Heather Schmidt1, Joelle Kalicki1, Qunyuan Zhang2,5, Lei Chen1, Ling Lin1, Michael C. Wendl1,2, Joshua F. McMichael1, Vincent J. Magrini1,2, Lisa Cook1, Sean D. McGrath1, Tammi L. Vickery1, Elizabeth Appelbaum1, Katherine DeSchryver3, Sherri Davies3, Therese Guintoli3, Li Lin3, Robert Crowder3, Yu Tao6, Jacqueline E. Snider3, Scott M. Smith1, Adam F. Dukes1, Gabriel E. Sanderson1, Craig S. Pohl1, Kim D. Delehaunty1, Catrina C. Fronick1, Kimberley A. Pape1, Jerry S. Reed1, Jody S. Robinson1, Jennifer S. Hodges1, William Schierding1, Nathan D. Dees1, Dong Shen1, Devin P. Locke1, Madeline E. Wiechert1, James M. Eldred1, Josh B. Peck1, Benjamin J. Oberkfell1, Justin T. Lolofie1, Feiyu Du1, Amy E. Hawkins1, Michelle D. O’Laughlin1, Kelly E. Bernard1, Mark Cunningham1, Glendoria Elliott1, Mark D. Mason1, Dominic M. Thompson Jr7, Jennifer L. Ivanovich7, Paul J. Goodfellow7, Charles M. Perou8, George M. Weinstock1,2, Rebecca Aft7, Mark Watson9, Timothy J. Ley1,2,3,4, Richard K. Wilson1,2,4 & Elaine R. Mardis1,2,4
1. The Genome Center at Washington University,
2. Department of Genetics,
3. Department of Medicine,
4. Siteman Cancer Center,
5. Division of Statistical Genomics,
6. Division of Biostatistics,
7. Department of Surgery and the Young Women’s Breast Cancer Program,
8. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63108, USA
9. Department of Genetics, Lineberger Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
10. These authors contributed equally to this work.
Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour.
