دورية أكاديمية
Exome sequencing characterizes the somatic mutation spectrum of early serrated lesions in a patient with serrated polyposis syndrome (SPS)
| العنوان: | Exome sequencing characterizes the somatic mutation spectrum of early serrated lesions in a patient with serrated polyposis syndrome (SPS) |
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| المؤلفون: | Sukanya Horpaopan, Jutta Kirfel, Sophia Peters, Michael Kloth, Robert Hüneburg, Janine Altmüller, Dmitriy Drichel, Margarete Odenthal, Glen Kristiansen, Christian Strassburg, Jacob Nattermann, Per Hoffmann, Peter Nürnberg, Reinhard Büttner, Holger Thiele, Philip Kahl, Isabel Spier, Stefan Aretz |
| المصدر: | Hereditary Cancer in Clinical Practice, Vol 15, Iss 1, Pp 1-10 (2017) |
| بيانات النشر: | BMC, 2017. |
| سنة النشر: | 2017 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens LCC:Genetics |
| مصطلحات موضوعية: | Familial colorectal cancer (CRC), Exome sequencing, Hyperplastic polyposis syndrome (HPS), Serrated polyposis syndrome (SPS), Serrated pathway, Somatic mutations, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Genetics, QH426-470 |
| الوصف: | 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 (~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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1897-4287 21676224 |
| Relation: | http://link.springer.com/article/10.1186/s13053-017-0082-9; https://doaj.org/toc/1897-4287 |
| DOI: | 10.1186/s13053-017-0082-9 |
| URL الوصول: | https://doaj.org/article/5480a21676224540bc4fbf489ce2257d |
| رقم الأكسشن: | edsdoj.5480a21676224540bc4fbf489ce2257d |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 18974287 21676224 |
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| DOI: | 10.1186/s13053-017-0082-9 |