Dataset Information

Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report.

ABSTRACT: The aim of this study was to verify the reliability of a next generation sequencing (NGS)-based method as a strategy to detect all possible BRCA mutations, including large genomic rearrangements. Genomic DNA was obtained from a peripheral blood sample provided by a patient from Southern Italy with early onset breast cancer and a family history of diverse cancers. BRCA molecular analysis was performed by NGS, and sequence data were analyzed using two software packages. Comparative genomic hybridization (CGH) array was used as confirmatory method. A novel large duplication, involving exons 4-26, of BRCA2 was directly detected in the patient by NGS workflow including quantitative analysis of copy number variants. The duplication observed was also found by CGH array, thus confirming its extent. Large genomic rearrangements can affect the BRCA1/2 genes, and thus contribute to germline predisposition to familial breast and ovarian cancers. The frequency of these mutations could be underestimated because of technical limitations of several routinely used molecular analysis, while their evaluation should be included also in these molecular testing. The NGS-based strategy described herein is an effective procedure to screen for all kinds of BRCA mutations.

SUBMITTER: Nunziato M

PROVIDER: S-EPMC5713453 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report.

Nunziato Marcella M Starnone Flavio F Lombardo Barbara B Pensabene Matilde M Condello Caterina C Verdesca Francesco F Carlomagno Chiara C De Placido Sabino S Pastore Lucio L Salvatore Francesco F D'Argenio Valeria V

International journal of molecular sciences 20171122 11

The aim of this study was to verify the reliability of a next generation sequencing (NGS)-based method as a strategy to detect all possible <i>BRCA</i> mutations, including large genomic rearrangements. Genomic DNA was obtained from a peripheral blood sample provided by a patient from Southern Italy with early onset breast cancer and a family history of diverse cancers. <i>BRCA</i> molecular analysis was performed by NGS, and sequence data were analyzed using two software packages. Comparative g ...[more]

PMID: 29165356

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Project description:BackgroundIn recent years more than 20 assemblers have been proposed to tackle the hard task of assembling NGS data. A common heuristic when assembling a genome is to use several assemblers and then select the best assembly according to some criteria. However, recent results clearly show that some assemblers lead to better statistics than others on specific regions but are outperformed on other regions or on different evaluation measures. To limit these problems we developed GAM-NGS (Genomic Assemblies Merger for Next Generation Sequencing), whose primary goal is to merge two or more assemblies in order to enhance contiguity and correctness of both. GAM-NGS does not rely on global alignment: regions of the two assemblies representing the same genomic locus (called blocks) are identified through reads' alignments and stored in a weighted graph. The merging phase is carried out with the help of this weighted graph that allows an optimal resolution of local problematic regions.ResultsGAM-NGS has been tested on six different datasets and compared to other assembly reconciliation tools. The availability of a reference sequence for three of them allowed us to show how GAM-NGS is a tool able to output an improved reliable set of sequences. GAM-NGS is also a very efficient tool able to merge assemblies using substantially less computational resources than comparable tools. In order to achieve such goals, GAM-NGS avoids global alignment between contigs, making its strategy unique among other assembly reconciliation tools.ConclusionsThe difficulty to obtain correct and reliable assemblies using a single assembler is forcing the introduction of new algorithms able to enhance de novo assemblies. GAM-NGS is a tool able to merge two or more assemblies in order to improve contiguity and correctness. It can be used on all NGS-based assembly projects and it shows its full potential with multi-library Illumina-based projects. With more than 20 available assemblers it is hard to select the best tool. In this context we propose a tool that improves assemblies (and, as a by-product, perhaps even assemblers) by merging them and selecting the generating that is most likely to be correct.

Dataset Information

Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report.

Publications

Fast Detection of a BRCA2 Large Genomic Duplication by Next Generation Sequencing as a Single Procedure: A Case Report.

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