人类乳腺癌和结直肠癌的基因组图谱。

The genomic landscapes of human breast and colorectal cancers.

作者信息

Wood Laura D, Parsons D Williams, Jones Siân, Lin Jimmy, Sjöblom Tobias, Leary Rebecca J, Shen Dong, Boca Simina M, Barber Thomas, Ptak Janine, Silliman Natalie, Szabo Steve, Dezso Zoltan, Ustyanksky Vadim, Nikolskaya Tatiana, Nikolsky Yuri, Karchin Rachel, Wilson Paul A, Kaminker Joshua S, Zhang Zemin, Croshaw Randal, Willis Joseph, Dawson Dawn, Shipitsin Michail, Willson James K V, Sukumar Saraswati, Polyak Kornelia, Park Ben Ho, Pethiyagoda Charit L, Pant P V Krishna, Ballinger Dennis G, Sparks Andrew B, Hartigan James, Smith Douglas R, Suh Erick, Papadopoulos Nickolas, Buckhaults Phillip, Markowitz Sanford D, Parmigiani Giovanni, Kinzler Kenneth W, Velculescu Victor E, Vogelstein Bert

机构信息

Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.

出版信息

Science. 2007 Nov 16;318(5853):1108-13. doi: 10.1126/science.1145720. Epub 2007 Oct 11.

DOI:10.1126/science.1145720

PMID:17932254

Abstract

Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.

摘要

人类癌症是由癌基因和肿瘤抑制基因中的突变积累引起的。为了编目肿瘤发生过程中发生的基因变化，我们从11个乳腺肿瘤和11个结肠直肠肿瘤中分离出DNA，并确定了这些样本中参考序列数据库中基因的序列。基于对代表18191个基因的20857个转录本的外显子的分析，我们得出结论，乳腺癌和结肠直肠癌的基因组图谱由少数常见突变的基因“山峰”和大量低频突变的基因“山丘”组成。我们描述了可能有助于识别在肿瘤发生中起作用的突变的统计和生物信息学工具。这些结果对于理解人类癌症的本质和异质性以及将个人基因组学用于肿瘤诊断和治疗具有重要意义。