The mutation spectrum revealed by paired genome sequences from a lung cancer patient.
In: Nature, Jg. 465 (2010-05-27), Heft 7297, S. 473-477
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Zugriff:
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. [ABSTRACT FROM AUTHOR]
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The mutation spectrum revealed by paired genome sequences from a lung cancer patient.
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Autor/in / Beteiligte Person: | 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. |
Zeitschrift: | Nature, Jg. 465 (2010-05-27), Heft 7297, S. 473-477 |
Veröffentlichung: | 2010 |
Medientyp: | academicJournal |
ISSN: | 0028-0836 (print) |
DOI: | 10.1038/nature09004 |
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