Massively parallel enrichment of low-frequency alleles enables duplex sequencing at low depth

Gydush, Gregory; Nguyen, Eileen; Bae, Jin H; Blewett, Timothy; Rhoades, Justin; Reed, Sarah C.; Shea, Douglas; Xiong, Kan; Liu, Ruolin; Yu, Fangyan; Leong, Ka Wai; Choudhury, Atish D.; Stover, Daniel G.; Tolaney, Sara M.; Krop, Ian E.; Love, J. Christopher; Parsons, Heather A.; Makrigiorgos, G. Mike; Golub, Todd R.; Adalsteinsson, Viktor A.

doi:10.1038/s41551-022-00855-9

Cited by 56 publications

(36 citation statements)

References 52 publications

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“…Mutationenrichment methods provide a unique solution in this case. To this end, an improved version of the DEASH method, termed MAESTRO [78], provides a feasible enrichment approach for large target duplex sequencing at low cost, thus providing both 'breadth and depth'. On the other hand, the NaME-PrO and pre-PCR-UVME methods provide multi-target enrichment principles that could potentially be applied to cfDNA directly and used with any downstream method, including NGS.…”

Section: Discussionmentioning

confidence: 99%

“…Although the originally described DEASH method was not applied on cfDNA samples, a recent development uses a modified DEASH principle to track thousands of low-level mutations in cfDNA. Minor-allele-enriched sequencing through recognition oligonucleotides (MAESTRO), employs short probes to capture up to 10,000 low-level mutations simultaneously, and then, incorporates duplex sequencing to detect mutation fingerprints in cfDNA for tracking minimal residual disease with high sensitivity and specificity (Figure 3B) [78].…”

Section: Deashmentioning

confidence: 99%

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Pre-PCR Mutation-Enrichment Methods for Liquid Biopsy Applications

Darbeheshti

Makrigiorgos

2022

Cancers

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Liquid biopsy is having a remarkable impact on healthcare- and disease-management in the context of personalized medicine. Circulating free DNA (cfDNA) is one of the most instructive liquid-biopsy-based biomarkers and harbors valuable information for diagnostic, predictive, and prognostic purposes. When it comes to cancer, circulating DNA from the tumor (ctDNA) has a wide range of applications, from early cancer detection to the early detection of relapse or drug resistance, and the tracking of the dynamic genomic make-up of tumor cells. However, the detection of ctDNA remains technically challenging, due, in part, to the low frequency of ctDNA among excessive circulating cfDNA originating from normal tissues. During the past three decades, mutation-enrichment methods have emerged to boost sensitivity and enable facile detection of low-level mutations. Although most developed techniques apply mutation enrichment during or following initial PCR, there are a few techniques that allow mutation selection prior to PCR, which provides advantages. Pre-PCR enrichment techniques can be directly applied to genomic DNA and diminish the influence of PCR errors that can take place during amplification. Moreover, they have the capability for high multiplexity and can be followed by established mutation detection and enrichment technologies without changes to their established procedures. The first approaches for pre-PCR enrichment were developed by employing restriction endonucleases directly on genomic DNA in the early 1990s. However, newly developed pre-PCR enrichment methods provide higher sensitivity and versatility. This review describes the available pre-PCR enrichment methods and focuses on the most recently developed techniques (NaME-PrO, UVME, and DEASH/MAESTRO), emphasizing their applications in liquid biopsies.

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Section: Discussionmentioning

confidence: 99%

Section: Deashmentioning

confidence: 99%

Pre-PCR Mutation-Enrichment Methods for Liquid Biopsy Applications

Darbeheshti

Makrigiorgos

2022

Cancers

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“…68,69 In spite of this interest; however, it is unclear if suitable markers are available for all patients and some guidelines only specify molecular targets for select patients. 70 To address this shortcoming, some groups propose approaches which include use of any somatic alteration as a potential target for monitoring 71,72 . These approaches highlight the power of a fully matched sample at initial tumor genotyping and the pitfalls of inaccurate somatic/germline assignment.…”

Section: Discussionmentioning

confidence: 99%

Enhanced clinical assessment of hematologic malignancies through routine paired tumor:normal sequencing

Ptashkin

Ewalt

Jayakumaran

et al. 2022

Preprint

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Genomic profiling of hematologic malignancies has augmented our understanding of variants that contribute to disease pathogenesis and supported development of prognostic models that inform disease management in the clinic. Tumor only sequencing assays are limited in their ability to identify definitive somatic variants, which can lead to ambiguity in clinical reporting and patient management. Here, we describe the MSK-IMPACT Heme cohort, a comprehensive data set of somatic alterations from paired tumor and normal DNA using a hybridization capture next generation sequencing platform. We highlight patterns of mutations, copy number alterations, and mutation signatures in a broad set of myeloid and lymphoid neoplasms. We also demonstrate the power of appropriate matching to make definitive somatic calls, including in patients who have undergone allogeneic stem cell transplant. We expect that this resource will further spur research into the pathobiology and clinical utility of clinical sequencing for patients with hematologic neoplasms.

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Section: Discussionmentioning

confidence: 99%

Enhanced clinical assessment of hematologic malignancies through routine paired tumor:normal sequencing

Ptashkin

Ewalt

Jayakumaran

et al. 2022

Preprint

View full text Add to dashboard Cite

Genomic profiling of hematologic malignancies has augmented our understanding of variants that contribute to disease pathogenesis and supported development of prognostic models that inform disease management in the clinic. Tumor only sequencing assays are limited in their ability to identify definitive somatic variants, which can lead to ambiguity in clinical reporting and patient management. Here, we describe the MSK-IMPACT Heme cohort, a comprehensive data set of somatic alterations from paired tumor and normal DNA using a hybridization capture-based next generation sequencing platform. We highlight patterns of mutations, copy number alterations, and mutation signatures in a broad set of myeloid and lymphoid neoplasms. We also demonstrate the power of appropriate matching to make definitive somatic calls, including in patients who have undergone allogeneic stem cell transplant. We expect that this resource will further spur research into the pathobiology and clinical utility of clinical sequencing for patients with hematologic neoplasms.

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Massively parallel enrichment of low-frequency alleles enables duplex sequencing at low depth

Cited by 56 publications

References 52 publications

Pre-PCR Mutation-Enrichment Methods for Liquid Biopsy Applications

Pre-PCR Mutation-Enrichment Methods for Liquid Biopsy Applications

Enhanced clinical assessment of hematologic malignancies through routine paired tumor:normal sequencing

Enhanced clinical assessment of hematologic malignancies through routine paired tumor:normal sequencing

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