Identification of Genomic Somatic Variants in Cancer

Fawcett, Gloria L.; Eterovic, Agda Karina

doi:10.1016/bs.acc.2016.07.006

Cited by 2 publications

(1 citation statement)

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“…However, these techniques produce overwhelming amounts of data that require extensive bioinformatics analyses [ 5 ]. Moreover, for proper interpretation of disease-associated somatic variations in the tumor DNA, sequencing of constitutive germline specimen from the same patient is essential [ 8 ]. In addition, high variability in mutation call rates and limited concordance among analysis pipelines have been reported in a comparative analysis of WGS data within the International Cancer Genome Consortium [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Multicenter validation of cancer gene panel-based next-generation sequencing for translational research and molecular diagnostics

et al. 2018

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The simultaneous detection of multiple somatic mutations in the context of molecular diagnostics of cancer is frequently performed by means of amplicon-based targeted next-generation sequencing (NGS). However, only few studies are available comparing multicenter testing of different NGS platforms and gene panels. Therefore, seven partner sites of the German Cancer Consortium (DKTK) performed a multicenter interlaboratory trial for targeted NGS using the same formalin-fixed, paraffin-embedded (FFPE) specimen of molecularly pre-characterized tumors (n = 15; each n = 5 cases of Breast, Lung, and Colon carcinoma) and a colorectal cancer cell line DNA dilution series. Detailed information regarding pre-characterized mutations was not disclosed to the partners. Commercially available and custom-designed cancer gene panels were used for library preparation and subsequent sequencing on several devices of two NGS different platforms. For every case, centrally extracted DNA and FFPE tissue sections for local processing were delivered to each partner site to be sequenced with the commercial gene panel and local bioinformatics. For cancer-specific panel-based sequencing, only centrally extracted DNA was analyzed at seven sequencing sites. Subsequently, local data were compiled and bioinformatics was performed centrally. We were able to demonstrate that all pre-characterized mutations were re-identified correctly, irrespective of NGS platform or gene panel used. However, locally processed FFPE tissue sections disclosed that the DNA extraction method can affect the detection of mutations with a trend in favor of magnetic bead-based DNA extraction methods. In conclusion, targeted NGS is a very robust method for simultaneous detection of various mutations in FFPE tissue specimens if certain pre-analytical conditions are carefully considered.

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Section: Introductionmentioning

confidence: 99%

Multicenter validation of cancer gene panel-based next-generation sequencing for translational research and molecular diagnostics

et al. 2018

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Next generation sequencing applications for cardiovascular disease

et al. 2017

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The Human Genome Project (HGP), as the primary sequencing of the human genome, lasted more than one decade to be completed using the traditional Sanger's method. At present, next-generation sequencing (NGS) technology could provide the genome sequence data in hours. NGS has also decreased the expense of sequencing; therefore, nowadays it is possible to carry out both whole-genome (WGS) and whole-exome sequencing (WES) for the variations detection in patients with rare genetic diseases as well as complex disorders such as common cardiovascular diseases (CVDs). Finding new variants may contribute to establishing a risk profile for the pathology process of diseases. Here, recent applications of NGS in cardiovascular medicine are discussed; both Mendelian disorders of the cardiovascular system and complex genetic CVDs including inherited cardiomyopathy, channelopathies, stroke, coronary artery disease (CAD) and are considered. We also state some future use of NGS in clinical practice for increasing our information about the CVDs genetics and the limitations of this new technology. Key messages Traditional Sanger's method was the mainstay for Human Genome Project (HGP); Sanger sequencing has high fidelity but is slow and costly as compared to next generation methods. Within cardiovascular medicine, NGS has been shown to be successful in identifying novel causative mutations and in the diagnosis of Mendelian diseases which are caused by a single variant in a single gene. NGS has provided the opportunity to perform parallel analysis of a great number of genes in an unbiased approach (i.e. without knowing the underlying biological mechanism) which probably contribute to advance our knowledge regarding the pathology of complex diseases such as CVD.

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Identification of Genomic Somatic Variants in Cancer

Cited by 2 publications

References 129 publications

Multicenter validation of cancer gene panel-based next-generation sequencing for translational research and molecular diagnostics

Multicenter validation of cancer gene panel-based next-generation sequencing for translational research and molecular diagnostics

Next generation sequencing applications for cardiovascular disease

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