کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151666 | 1090012 | 2012 | 19 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Single Nucleotide Polymorphism Microarray Analysis in Cortisol-Secreting Adrenocortical Adenomas Identifies New Candidate Genes and Pathways
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کلمات کلیدی
ACCCNAACAqRT-PCRCGHAdrenocortical adenoma - آدنوم آدنوکورتیکloss of heterozygosity - از دست دادن هتروزیگوتیسمupd - به روز رسانیcomparative genomic hybridization - ترکیب هیبریداسیون ژنومی مقایسه شدهUniparental disomy - فساد اداریfluorescence in situ hybridization - فلورسانس در هیبریداسیون در محلLOH - لوهانFish - ماهیquantitative real-time polymerase chain reaction - واکنش زنجیره ای پلیمراز کمی زمان واقعی استSingle nucleotide polymorphism - پلیمورفیسم تک نوکلئوتیدیSNP - چندریختی تک-نوکلئوتیدAdrenocortical carcinoma - کارسینوم عروق کرونرCopy number alteration - کپی تغییر شماره
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The genetic mechanisms underlying adrenocortical tumor development are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays (Affymetrix SNP 6.0) to detect copy number alterations (CNAs) and copy-neutral losses of heterozygosity (cnLOH) in 15 cortisol-secreting adrenocortical adenomas with matched blood samples. We focused on microalterations aiming to discover new candidate genes involved in early tumorigenesis and/or autonomous cortisol secretion. We identified 962 CNAs with a median of 18 CNAs per sample. Half of them involved noncoding regions, 89% were less than 100 kb, and 28% were found in at least two samples. The most frequently gained regions were 5p15.33, 6q16.1, 7p22.3-22.2, 8q24.3, 9q34.2-34.3, 11p15.5, 11q11, 12q12, 16q24.3, 20p11.1-20q21.11, and Xq28 (â¥20% of cases), most of them being identified in the same three adenomas. These regions contained among others genes like NOTCH1, CYP11B2, HRAS, and IGF2. Recurrent losses were less common and smaller than gains, being mostly localized at 1p, 6q, and 11q. Pathway analysis revealed that Notch signaling was the most frequently altered. We identified 46 recurrent CNAs that each affected a single gene (31 gains and 15 losses), including genes involved in steroidogenesis (CYP11B1) or tumorigenesis (CTNNB1, EPHA7, SGK1, STIL, FHIT). Finally, 20 small cnLOH in four cases affecting 15 known genes were found. Our findings provide the first high-resolution genome-wide view of chromosomal changes in cortisol-secreting adenomas and identify novel candidate genes, such as HRAS, EPHA7, and SGK1. Furthermore, they implicate that the Notch1 signaling pathway might be involved in the molecular pathogenesis of adrenocortical tumors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 14, Issue 3, March 2012, Pages 206-218, IN8-IN13
Journal: Neoplasia - Volume 14, Issue 3, March 2012, Pages 206-218, IN8-IN13
نویسندگان
Cristina L. Ronchi, Ellen Leich, Silviu Sbiera, Dirk Weismann, Andreas Rosenwald, Bruno Allolio, Martin Fassnacht,