| Autor: |
Huiling He, Wei Li, Dayong Wu, Rebecca Nagy, Sandya Liyanarachchi, Keiko Akagi, Jaroslaw Jendrzejewski, Hong Jiao, Kevin Hoag, Bernard Wen, Mukund Srinivas, Gavisha Waidyaratne, Rui Wang, Anna Wojcicka, Ilene R Lattimer, Elzbieta Stachlewska, Malgorzata Czetwertynska, Joanna Dlugosinska, Wojciech Gierlikowski, Rafal Ploski, Marek Krawczyk, Krystian Jazdzewski, Juha Kere, David E Symer, Victor Jin, Qianben Wang, Albert de la Chapelle |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Předmět: |
|
| Zdroj: |
PLoS ONE, Vol 8, Iss 5, p e61920 (2013) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0061920 |
| Popis: |
Thyroid cancer shows high heritability but causative genes remain largely unknown. According to a common hypothesis the genetic predisposition to thyroid cancer is highly heterogeneous; being in part due to many different rare alleles. Here we used linkage analysis and targeted deep sequencing to detect a novel single-nucleotide mutation in chromosome 4q32 (4q32A>C) in a large pedigree displaying non-medullary thyroid carcinoma (NMTC). This mutation is generally ultra-rare; it was not found in 38 NMTC families, in 2676 sporadic NMTC cases or 2470 controls. The mutation is located in a long-range enhancer element whose ability to bind the transcription factors POU2F and YY1 is significantly impaired, with decreased activity in the presence of the C- allele compared with the wild type A-allele. An enhancer RNA (eRNA) is transcribed in thyroid tissue from this region and is greatly downregulated in NMTC tumors. We suggest that this is an example of an ultra-rare mutation predisposing to thyroid cancer with high penetrance. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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