Ultra-Rare Mutation in Long-Range Enhancer Predisposes to Thyroid Carcinoma with High Penetrance
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{"title"=>"Ultra-Rare Mutation in Long-Range Enhancer Predisposes to Thyroid Carcinoma with High Penetrance", "type"=>"journal", "authors"=>[{"first_name"=>"Huiling", "last_name"=>"He", "scopus_author_id"=>"7402291708"}, {"first_name"=>"Wei", "last_name"=>"Li", "scopus_author_id"=>"56191636800"}, {"first_name"=>"Dayong", "last_name"=>"Wu", "scopus_author_id"=>"48061686400"}, {"first_name"=>"Rebecca", "last_name"=>"Nagy", "scopus_author_id"=>"8547773700"}, {"first_name"=>"Sandya", "last_name"=>"Liyanarachchi", "scopus_author_id"=>"6506509119"}, {"first_name"=>"Keiko", "last_name"=>"Akagi", "scopus_author_id"=>"7102392372"}, {"first_name"=>"Jaroslaw", "last_name"=>"Jendrzejewski", "scopus_author_id"=>"41861840300"}, {"first_name"=>"Hong", "last_name"=>"Jiao", "scopus_author_id"=>"7102775038"}, {"first_name"=>"Kevin", "last_name"=>"Hoag", "scopus_author_id"=>"55699165800"}, {"first_name"=>"Bernard", "last_name"=>"Wen", "scopus_author_id"=>"48461949100"}, {"first_name"=>"Mukund", "last_name"=>"Srinivas", "scopus_author_id"=>"55699962800"}, {"first_name"=>"Gavisha", "last_name"=>"Waidyaratne", "scopus_author_id"=>"55700723800"}, {"first_name"=>"Rui", "last_name"=>"Wang", "scopus_author_id"=>"14026199600"}, {"first_name"=>"Anna", "last_name"=>"Wojcicka", "scopus_author_id"=>"6508272159"}, {"first_name"=>"Ilene R.", "last_name"=>"Lattimer", "scopus_author_id"=>"55985503200"}, {"first_name"=>"Elzbieta", "last_name"=>"Stachlewska", "scopus_author_id"=>"8537964200"}, {"first_name"=>"Malgorzata", "last_name"=>"Czetwertynska", "scopus_author_id"=>"23495633400"}, {"first_name"=>"Joanna", "last_name"=>"Dlugosinska", "scopus_author_id"=>"15122097000"}, {"first_name"=>"Wojciech", "last_name"=>"Gierlikowski", "scopus_author_id"=>"55699401300"}, {"first_name"=>"Rafal", "last_name"=>"Ploski", "scopus_author_id"=>"7003937391"}, {"first_name"=>"Marek", "last_name"=>"Krawczyk", "scopus_author_id"=>"55584225700"}, {"first_name"=>"Krystian", "last_name"=>"Jazdzewski", "scopus_author_id"=>"6603806865"}, {"first_name"=>"Juha", "last_name"=>"Kere", "scopus_author_id"=>"56095225300"}, {"first_name"=>"David E.", "last_name"=>"Symer", "scopus_author_id"=>"6602831373"}, {"first_name"=>"Victor", "last_name"=>"Jin", "scopus_author_id"=>"26636467700"}, {"first_name"=>"Qianben", "last_name"=>"Wang", "scopus_author_id"=>"8694228900"}, {"first_name"=>"Albert", "last_name"=>"de la Chapelle", "scopus_author_id"=>"35393340400"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23690926", "sgr"=>"84877788249", "doi"=>"10.1371/journal.pone.0061920", "scopus"=>"2-s2.0-84877788249", "pui"=>"368920825", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)", "issn"=>"19326203"}, "id"=>"12ec9a89-2d9c-3858-bbae-f33738f6a6fc", "abstract"=>"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. 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Scopus | Further Information

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Relative Metric

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