We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The mutation spectrum revealed by paired genome sequences from a lung cancer patient.
- Authors
Lee, William; Jiang, Zhaoshi; Liu, Jinfeng; Haverty, Peter M.; Guan, Yinghui; Stinson, Jeremy; Yue, Peng; Zhang, Yan; Pant, Krishna P.; Bhatt, Deepali; Ha, Connie; Johnson, Stephanie; Kennemer, Michael I.; Mohan, Sankar; Nazarenko, Igor; Watanabe, Colin; Sparks, Andrew B.; Shames, David S.; Gentleman, Robert; de Sauvage, Frederic J.
- Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung carcinomas in smokers being the predominant form of the disease. Although previous studies have identified important common somatic mutations in lung cancers, they have primarily focused on a limited set of genes and have thus provided a constrained view of the mutational spectrum. Recent cancer sequencing efforts have used next-generation sequencing technologies to provide a genome-wide view of mutations in leukaemia, breast cancer and cancer cell lines. Here we present the complete sequences of a primary lung tumour (60× coverage) and adjacent normal tissue (46×). Comparing the two genomes, we identify a wide variety of somatic variations, including >50,000 high-confidence single nucleotide variants. We validated 530 somatic single nucleotide variants in this tumour, including one in the KRAS proto-oncogene and 391 others in coding regions, as well as 43 large-scale structural variations. These constitute a large set of new somatic mutations and yield an estimated 17.7 per megabase genome-wide somatic mutation rate. Notably, we observe a distinct pattern of selection against mutations within expressed genes compared to non-expressed genes and in promoter regions up to 5 kilobases upstream of all protein-coding genes. Furthermore, we observe a higher rate of amino acid-changing mutations in kinase genes. We present a comprehensive view of somatic alterations in a single lung tumour, and provide the first evidence, to our knowledge, of distinct selective pressures present within the tumour environment.
- Subjects
LUNG cancer; CANCER-related mortality; CIGARETTE smokers; ANTIBODY diversity; LEUKEMIA; BREAST cancer; CANCER cells; GENOMES; NUCLEOTIDES; TUMORS
- Publication
Nature, 2010, Vol 465, Issue 7297, p473
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature09004