dc.contributor.author
Timmermann, Bernd
dc.contributor.author
Kerick, Martin
dc.contributor.author
Roehr, Christina
dc.contributor.author
Fischer, Axel
dc.contributor.author
Isau, Melanie
dc.contributor.author
Boerno, Stefan T.
dc.contributor.author
Wunderlich, Andrea
dc.contributor.author
Barmeyer, Christian
dc.contributor.author
Seemann, Petra
dc.contributor.author
Koenig, Jana
dc.contributor.author
Lappe, Michael
dc.contributor.author
Kuss, Andreas W.
dc.contributor.author
Garshasbi, Masoud
dc.contributor.author
Bertram, Lars
dc.contributor.author
Trappe, Kathrin
dc.contributor.author
Werber, Martin
dc.contributor.author
Herrmann, Bernhard G.
dc.contributor.author
Zatloukal, Kurt
dc.contributor.author
Lehrach, Hans
dc.contributor.author
Schweiger, Michal R.
dc.date.accessioned
2018-06-08T04:16:20Z
dc.date.available
2015-11-24T08:47:56.368Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/16945
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-21126
dc.description.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.
en
dc.rights.uri
http://creativecommons.org/licenses/by/2.0/de/
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie
dc.title
Somatic Mutation Profiles of MSI and MSS Colorectal Cancer Identified by Whole
Exome Next Generation Sequencing and Bioinformatics Analysis
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
PLoS ONE. - 5 (2010), 12, Artikel Nr. e15661
dcterms.bibliographicCitation.doi
10.1371/journal.pone.0015661
dcterms.bibliographicCitation.url
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0015661
refubium.affiliation
Biologie, Chemie, Pharmazie
de
refubium.mycore.fudocsId
FUDOCS_document_000000023518
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000005705
dcterms.accessRights.openaire
open access