Universität zu Köln

Horpaopan, Sukanya, Kirfel, Jutta, Peters, Sophia, Kloth, Michael, Hueneburg, Robert, Altmueller, Janine, Drichel, Dmitriy ORCID: 0000-0001-5978-3458, Odenthal, Margarete, Kristiansen, Glen, Strassburg, Christian, Nattermann, Jacob, Hoffmann, Per, Nuernberg, Peter, Buettner, Reinhard, Thiele, Holger, Kahl, Philip, Spier, Isabel and Aretz, Stefan ORCID: 0000-0002-5228-1890 (2017). Exome sequencing characterizes the somatic mutation spectrum of early serrated lesions in a patient with serrated polyposis syndrome (SPS). Hered. Cancer Clin. Pract., 15. LONDON: BIOMED CENTRAL LTD. ISSN 1897-4287

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Abstract

Background: Serrated or Hyperplastic Polyposis Syndrome (SPS, HPS) is a yet poorly defined colorectal cancer (CRC) predisposition characterised by the occurrence of multiple and/or large serrated polyps throughout the colon. A serrated polyp-CRC sequence (serrated pathway) of CRC formation has been postulated, however, to date only few molecular signatures of serrated neoplasia (BRAF, KRAS, RNF43 mutations, CpG Island Methylation, MSI) have been described in a subset of SPS patients and neither the etiology of the syndrome nor the distinct genetic alterations during tumorigenesis have been identified. Methods: To identify somatic point mutations in potential novel candidate genes of SPS-associated lesions and the involved pathways we performed exome sequencing of eleven early serrated polyps obtained from a 41 year-old female patient with clinically confirmed SPS. For data filtering and analysis, standard pipelines were used. Somatic mutations were identified by comparison with leukocyte DNA and were validated by Sanger sequencing. Results: The BRAF p.V600E or KRAS p.G12D mutation was identified in six polyps (similar to 50%) and not found in polyps from the distal colon. In addition, we found seven unique rare somatic alterations of seven different genes in four serrated tumours, all of which are missense variants. The variant in ABI3BP and CATSPERB are predicted to be deleterious. No established cancer gene or candidate genes related to serrated tumorigenesis were affected. Conclusions: Somatic mutations seem to be rare events in early hyperplastic and serrated lesions of SPS patients. Neither frequently affected genes nor enrichment of specific pathways were observed. Thus, other alterations such as non-coding variants or epigenetic changes might be the major driving force of tumour progression in SPS.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Horpaopan, Sukanya UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirfel, Jutta UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, Sophia UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloth, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Hueneburg, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Drichel, Dmitriy UNSPECIFIED orcid.org/0000-0001-5978-3458 UNSPECIFIED Odenthal, Margarete UNSPECIFIED UNSPECIFIED UNSPECIFIED Kristiansen, Glen UNSPECIFIED UNSPECIFIED UNSPECIFIED Strassburg, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Nattermann, Jacob UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Per UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Kahl, Philip UNSPECIFIED UNSPECIFIED UNSPECIFIED Spier, Isabel UNSPECIFIED UNSPECIFIED UNSPECIFIED Aretz, Stefan UNSPECIFIED orcid.org/0000-0002-5228-1890 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-210842
DOI:	10.1186/s13053-017-0082-9
Journal or Publication Title:	Hered. Cancer Clin. Pract.
Volume:	15
Date:	2017
Publisher:	BIOMED CENTRAL LTD
Place of Publication:	LONDON
ISSN:	1897-4287
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COLORECTAL-CANCER PATHOGENESIS; MICROSATELLITE INSTABILITY; HYPERPLASTIC POLYPS; MOLECULAR-FEATURES; GENE-EXPRESSION; LUNG-CANCER; TARSH GENE; DNA; BRAF; SENESCENCE Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21084