Common Genetic Variants of MUTYH are not Associated with Cutaneous Malignant Melanoma: Application of Molecular Screening by Means of High-Resolution Melting Technique in a Pilot Case-Control Study

2011 ◽  
Vol 26 (1) ◽  
pp. 37-42 ◽  
Author(s):  
Concetta Santonocito ◽  
Andrea Paradisi ◽  
Rodolfo Capizzi ◽  
Eleonora Torti ◽  
Sara Lanza-Silveri ◽  
...  
Keyword(s):  
High Resolution ◽  
High Resolution Melting ◽  
Direct Sequencing ◽  
Strong Association ◽  
Laboratory Data ◽  
Gene Mutations ◽  
Case Control ◽  
Common Genetic Variants ◽  
Mutyh Gene ◽  
Embryonic Origin

MUTYH glycosylase recognizes the 8-oxoG:A mismatch and is able to excise the adenine base using proofreading mechanisms. Some papers have reported a strong association between cancer development or aggressiveness and MUTYH gene mutations. The aim of this study was to find a possible association between the most frequent MUTYH mutations and melanoma in the context of a case-control pilot study. One hundred ninety-five melanoma patients and 195 healthy controls were matched for sex and age. Clinical and laboratory data were collected in a specific database and all individuals were analyzed for MUTYH mutations by high-resolution melting and direct sequencing techniques. Men and women had significantly different distributions of tumor sites and phototypes. No significant associations were observed between the Y165C, G382D and V479F MUTYH mutations and risk of melanoma development or aggressiveness. Our preliminary findings therefore do not confirm a role for MUTYH gene mutations in the melanoma risk. Further studies are necessary for the assessment of MUTYH not only in melanoma but also other cancer types with the same embryonic origin, in the context of larger arrays studies of genes involved in DNA stability or integrity.

scholarly journals Parental mosaicism in Marfan and Ehlers–Danlos syndromes and related disorders

2021 ◽  
Author(s):  
Bertrand Chesneau ◽  
Aurélie Plancke ◽  
Guillaume Rolland ◽  
Nicolas Chassaing ◽  
Christine Coubes ◽  
...  
Keyword(s):  
High Resolution ◽  
Marfan Syndrome ◽  
High Resolution Melting ◽  
De Novo ◽  
Direct Sequencing ◽  
Causal Variant ◽  
Connective Tissue Disorder ◽  
High Resolution Melting Analysis ◽  
Aortic Diseases ◽  
Melting Analysis

AbstractMarfan syndrome (MFS) is a heritable connective tissue disorder (HCTD) caused by pathogenic variants in FBN1 that frequently occur de novo. Although individuals with somatogonadal mosaicisms have been reported with respect to MFS and other HCTD, the overall frequency of parental mosaicism in this pathology is unknown. In an attempt to estimate this frequency, we reviewed all the 333 patients with a disease-causing variant in FBN1. We then used direct sequencing, combined with High Resolution Melting Analysis, to detect mosaicism in their parents, complemented by NGS when a mosaicism was objectivized. We found that (1) the number of apparently de novo events is much higher than the classically admitted number (around 50% of patients and not 25% as expected for FBN1) and (2) around 5% of the FBN1 disease-causing variants were not actually de novo as anticipated, but inherited in a context of somatogonadal mosaicisms revealed in parents from three families. High Resolution Melting Analysis and NGS were more efficient at detecting and evaluating the level of mosaicism compared to direct Sanger sequencing. We also investigated individuals with a causal variant in another gene identified through our “aortic diseases genes” NGS panel and report, for the first time, on an individual with a somatogonadal mosaicism in COL5A1. Our study shows that parental mosaicism is not that rare in Marfan syndrome and should be investigated with appropriate methods given its implications in patient’s management.

Identification of fibrillin-1 gene mutations in Marfan syndrome by high-resolution melting analysis

2009 ◽  
Vol 389 (2) ◽  
pp. 102-106 ◽  
Author(s):  
Chia-Cheng Hung ◽  
Shin-Yu Lin ◽  
Chien-Nan Lee ◽  
Hui-Yu Cheng ◽  
Chiou-Ya Lin ◽  
...  
Keyword(s):  
High Resolution ◽  
Marfan Syndrome ◽  
High Resolution Melting ◽  
Gene Mutations ◽  
High Resolution Melting Analysis ◽  
Fibrillin 1 ◽  
Melting Analysis

Detection of SF3B3 Gene Mutations in Oral Cancer by High Resolution Melting Analysis

2014 ◽  
Vol 60 (12/2014) ◽  
Author(s):  
Chun-Chi Chang ◽  
Ya-Sian Chang ◽  
Wen-Ling Chan ◽  
Kun-Tu Yeh ◽  
Ren-Jeng Wei ◽  
...  
Keyword(s):  
High Resolution ◽  
Oral Cancer ◽  
High Resolution Melting ◽  
Gene Mutations ◽  
High Resolution Melting Analysis ◽  
Melting Analysis

scholarly journals High resolution melting analysis for a rapid identification of heterozygous and homozygous sequence changes in the MUTYH gene

BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Rossella Tricarico ◽  
Francesca Crucianelli ◽  
Antonio Alvau ◽  
Claudio Orlando ◽  
Roberta Sestini ◽  
...  
Keyword(s):  
High Resolution ◽  
High Resolution Melting ◽  
Rapid Identification ◽  
High Resolution Melting Analysis ◽  
Mutyh Gene ◽  
Melting Analysis

scholarly journals Identifying Common Genetic Variants by High-Resolution Melting

2007 ◽  
Vol 53 (7) ◽  
pp. 1191-1198 ◽  
Author(s):  
Joshua G Vandersteen ◽  
Pinar Bayrak-Toydemir ◽  
Robert A Palais ◽  
Carl T Wittwer
Keyword(s):  
High Resolution ◽  
High Resolution Melting ◽  
False Negative ◽  
Melting Curve ◽  
High Resolution Melting Analysis ◽  
Common Variants ◽  
Difference Analysis ◽  
Common Genetic Variants ◽  
Blinded Study ◽  
Melting Analysis

Abstract Background: Heteroduplex scanning techniques usually detect all heterozygotes, including common variants not of clinical interest. Methods: We conducted high-resolution melting analysis on the 24 exons of the ACVRL1 and ENG genes implicated in hereditary hemorrhagic telangiectasia (HHT). DNA in samples from 13 controls and 19 patients was PCR amplified in the presence of LCGreen® I, and all 768 exons melted in an HR-1® instrument. We used 10 wild-type controls to identify common variants, and the remaining samples were blinded, amplified, and analyzed by melting curve normalization and overlay. Unlabeled probes characterized the sequence of common variants. Results: Eleven common variants were associated with 8 of the 24 HHT exons, and 96% of normal samples contained at least 1 variant. As a result, the positive predictive value (PPV) of a heterozygous exon was low (31%), even in a population of predominantly HHT patients. However, all common variants produced unique amplicon melting curves that, when considered and eliminated, resulted in a PPV of 100%. In our blinded study, 3 of 19 heterozygous disease-causing variants were missed; however, 2 were clerical errors, and the remaining false negative would have been identified by difference analysis. Conclusions: High-resolution melting analysis is a highly accurate heteroduplex scanning technique. With many exons, however, use of single-sample instruments may lead to clerical errors, and routine use of difference analysis is recommended. Common variants can be identified by their melting curve profiles and genotyped with unlabeled probes, greatly reducing the false-positive results common with scanning techniques.

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