Sequencing Structural Variants in Cancer for Precision Therapeutics

Macintyre, Geoff; Ylstra, Bauke; Brenton, James D.

doi:10.1016/j.tig.2016.07.002

Cited by 89 publications

(83 citation statements)

References 106 publications

(97 reference statements)

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“…The mutations in EZH2 are largely clustered in codon Y646 (Online Supplementary Figure S1) and are therefore technically very easily amenable to simple polymerase chain reaction (PCR) techniques, 55 while chromosomal gains can be monitored using fluorescence in situ hybridization (FISH) or NGS. 56,57 This signifies that EZH2 mutation status and chromosome 18 gain have a high potential for clinical implementation, in contrast to the microenvironment population markers CD8 and CD163. With current techniques, even if optimized, the absolute quantitative differences are too small between these 2 extreme cohorts to become a powerful and clinically useful tool for the scores around the cut point.…”

Section: P-value and Fdrmentioning

confidence: 99%

Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: a study by the Lunenburg Lymphoma Biomarker Consortium

et al. 2017

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In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a validation study evaluating published markers. To maximize sensitivity, an end of spectrum design was applied for 122 uniformly immunochemotherapy-treated follicular lymphoma patients retrieved from international trials and registries. The criteria were: early failure, progression or lymphoma-related death <2 years versus long remission, response duration of >5 years. Immunohistochemical staining for T cells and macrophages was performed on tissue microarrays from initial biopsies and scored with a validated computer-assisted protocol. Shallow whole-genome and deep targeted sequencing was performed on the same samples. The 96/122 cases with complete molecular and immunohistochemical data were included in the analysis. EZH2 wild-type ( P =0.006), gain of chromosome 18 ( P =0.002), low percentages of CD8+ cells ( P =0.011) and CD163+ areas ( P =0.038) were associated with early failure. No significant differences in other markers were observed, thereby refuting previous claims of their prognostic significance. Using an optimized study design, this Lunenburg Lymphoma Biomarker Consortium study substantiates wild-type EZH2 status, gain of chromosome 18, low percentages of CD8+ cells and CD163+ area as predictors of early failure to immunochemotherapy in follicular lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP [-like]), while refuting the prognostic impact of various other markers.

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Section: P-value and Fdrmentioning

confidence: 99%

Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: a study by the Lunenburg Lymphoma Biomarker Consortium

et al. 2017

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“…BiSeqS can complement screening for other genomic alterations, such as structural variants (SVs), for rare allele detection and monitoring (52). SVs provide exquisitely specific markers for cancer that can be used for liquid biopsies (9,50).…”

Section: Discussionmentioning

confidence: 99%

Bisulfite-converted duplexes for the strand-specific detection and quantification of rare mutations

Mattox

Wang

Springer

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The identification of mutations that are present at low frequencies in clinical samples is an essential component of precision medicine. The development of molecular barcoding for next-generation sequencing has greatly enhanced the sensitivity of detecting such mutations by massively parallel sequencing. However, further improvements in specificity would be useful for a variety of applications. We herein describe a technology (BiSeqS) that can increase the specificity of sequencing by at least two orders of magnitude over and above that achieved with molecular barcoding and can be applied to any massively parallel sequencing instrument. BiSeqS employs bisulfite treatment to distinguish the two strands of molecularly barcoded DNA; its specificity arises from the requirement for the same mutation to be identified in both strands. Because no library preparation is required, the technology permits very efficient use of the template DNA as well as sequence reads, which are nearly all confined to the amplicons of interest. Such efficiency is critical for clinical samples, such as plasma, in which only tiny amounts of DNA are often available. We show here that BiSeqS can be applied to evaluate transversions, as well as small insertions or deletions, and can reliably detect one mutation among >10,000 wild-type molecules.next-generation sequencing | bisulfite sequencing | strand-specificity | polymerase chain reaction | mutation

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“…Owing to the rapid evolution of next generation sequencing, the past decade has seen the characterization of nucleic acidboth somatic and/or germline alterations in a wide range of cancers generating a large body of information pertaining to how cancer develops, evolves, and reacts to various treatment modalities [Macintyre et al, 2016]. Also, a considerable number of genomic variants have been previously been reported to be causative of, or associated with, tumor progression or an increased risk for various types of cancer [Hanahan and Weinberg, 2011].…”

Section: Cancer Genomics Working Groupmentioning

confidence: 99%

The Genomic Medicine Alliance: A Global Effort to Facilitate the Introduction of Genomics into Healthcare in Developing Nations

Cooper

Mitropoulou

Brand

et al. 2018

Genomic Medicine in Emerging Economies

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The primary goal of genomic medicine is to make use of and examine thean individua l's genomic information to support the clinical decision-making process. At present, several international organizations and research consortia exist, which aim to support the translation of genomic research into clinical practice so that genomic medicine can ultimately be used to benefit the global community. Genomics, offers members a highly respected publication forum for reviews, original research findings and policy in this field. In the short-to-medium term, the Genomic Medicine Alliance aims to promote research collaborations between developed and developing countries and to organize educational activities in the field of genomic medicine. In the longer term, it aspires to become a focal point for global collaboration in the field of genomic medicine while helping to pave the way for a smoother transition from genomics research to genomic medicine.

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Sequencing Structural Variants in Cancer for Precision Therapeutics

Cited by 89 publications

References 106 publications

Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: a study by the Lunenburg Lymphoma Biomarker Consortium

Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: a study by the Lunenburg Lymphoma Biomarker Consortium

Bisulfite-converted duplexes for the strand-specific detection and quantification of rare mutations

The Genomic Medicine Alliance: A Global Effort to Facilitate the Introduction of Genomics into Healthcare in Developing Nations

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