کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2146940 | 1548388 | 2009 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
cDNA analysis demonstrates that the BRCA2 intronic variant IVS4-12del5 is a deleterious mutation
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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![عکس صفحه اول مقاله: cDNA analysis demonstrates that the BRCA2 intronic variant IVS4-12del5 is a deleterious mutation cDNA analysis demonstrates that the BRCA2 intronic variant IVS4-12del5 is a deleterious mutation](/preview/png/2146940.png)
چکیده انگلیسی
Mutation screening of the breast and ovarian cancer predisposition genes BRCA1 and BRCA2 is becoming an increasingly important part of clinical practice. Classification of rare non-truncating sequence variants in the BRCA1 and BRCA2 genes is problematic because it is not known whether these subtle changes alter function sufficiently to predispose cells to cancer development. Several studies have reported the biochemical analysis of BRCA2 variants, which disrupted the 5â² and 3â²splicing consensus elements (the GU-AG rule). However, little has been done to look into the consequences of variants located outside the 5â² and 3â² consensus splice sites. cDNA analysis demonstrates that the BRCA2*IVS4-12del5 splice site variant results in the deletion of exon 5, and the gene putatively produces a truncated BRCA2 protein of 164 amino acids instead of 3418 with the incorporation of 22 out of frame amino acids. The pattern of breast, melanoma, and pancreatic cancers in the paternal kindred is consistent with autosomal dominant inheritance of a deleterious BRCA2 mutation. Analysis of a tumor specimen indicates loss of heterozygosity (LOH). Sequence alignment indicates the deleted region is well conserved across different species. These results support the conclusion that BRCA2 IVS4-12del5 is a deleterious mutation. This study will shed light on the reclassification of intronic variants that do not disrupt the 5â² and 3â² splice sites (the GU-AG rule).
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis - Volume 663, Issues 1â2, 26 April 2009, Pages 84-89
Journal: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis - Volume 663, Issues 1â2, 26 April 2009, Pages 84-89
نویسندگان
Liying Zhang, Ruben Bacares, Sherry Boyar, Clifford Hudis, Khedoudja Nafa, Kenneth Offit,