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  Somatic mutation profiles of MSI and MSS colorectal cancer identified by whole exome next generation sequencing and bioinformatics analysis

Timmermann, B., Kerick, M., Roehr, C., Fischer, A., Isau, M., Boerno, S. T., et al. (2010). Somatic mutation profiles of MSI and MSS colorectal cancer identified by whole exome next generation sequencing and bioinformatics analysis. PLoS ONE, 5(12), e15661-e15661. doi:10.1371/journal.pone.0015661.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-79C7-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-79C9-4
Genre: Journal Article
Alternative Title : PLoS ONE

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Timmermann, B.1, Author              
Kerick, M.2, Author              
Roehr, C.2, Author              
Fischer, A.2, Author              
Isau, M.2, Author              
Boerno, S. T.3, Author
Wunderlich, A.2, Author              
Barmeyer, C., Author
Seemann, P.4, Author              
Koenig, J.3, Author
Lappe, M.5, Author              
Kuss, A. W.6, Author              
Garshasbi, M.7, Author              
Bertram, L.8, Author              
Trappe, K.3, Author
Werber, M.9, Author              
Herrmann, B. G.9, Author              
Zatloukal, K., Author
Lehrach, H.10, Author              
Schweiger, M. R.2, Author              
This work was supported by the German Federal Ministry of Education and Research (01GS08105 “Mutanom,” 01GS08111 “Intestinal Modifers”) and the Max Planck Society., Editor               more..
Affiliations:
1Sequencing, Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433559              
2Cancer Genomics (Michal-Ruth Schweiger), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479649              
3Max Planck Society, ou_persistent13              
4Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
5Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433554              
6Familial Cognitive Disorders (Luciana Musante), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479644              
7Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              
8Neuropsychiatric Genetics (Lars Bertram), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479655              
9Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              
10Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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 Abstract: BACKGROUND: Colorectal cancer (CRC) is with approximately 1 million cases the third most common cancer worldwide. Extensive research is ongoing to decipher the underlying genetic patterns with the hope to improve early cancer diagnosis and treatment. In this direction, the recent progress in next generation sequencing technologies has revolutionized the field of cancer genomics. However, one caveat of these studies remains the large amount of genetic variations identified and their interpretation. METHODOLOGY/PRINCIPAL FINDINGS: Here we present the first work on whole exome NGS of primary colon cancers. We performed 454 whole exome pyrosequencing of tumor as well as adjacent not affected normal colonic tissue from microsatellite stable (MSS) and microsatellite instable (MSI) colon cancer patients and identified more than 50,000 small nucleotide variations for each tissue. According to predictions based on MSS and MSI pathomechanisms we identified eight times more somatic non-synonymous variations in MSI cancers than in MSS and we were able to reproduce the result in four additional CRCs. Our bioinformatics filtering approach narrowed down the rate of most significant mutations to 359 for MSI and 45 for MSS CRCs with predicted altered protein functions. In both CRCs, MSI and MSS, we found somatic mutations in the intracellular kinase domain of bone morphogenetic protein receptor 1A, BMPR1A, a gene where so far germline mutations are associated with juvenile polyposis syndrome, and show that the mutations functionally impair the protein function. CONCLUSIONS/SIGNIFICANCE: We conclude that with deep sequencing of tumor exomes one may be able to predict the microsatellite status of CRC and in addition identify potentially clinically relevant mutations.

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Language(s): eng - English
 Dates: 2010-12-10
 Publication Status: Published in print
 Pages: -
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 Identifiers: eDoc: 548983
DOI: 10.1371/journal.pone.0015661
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Title: PLoS ONE
  Alternative Title : PLoS ONE
Source Genre: Journal
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Pages: - Volume / Issue: 5 (12) Sequence Number: - Start / End Page: e15661 - e15661 Identifier: ISSN: 1932-6203