Quantification of JAK2V617F mutation by next‐generation sequencing technology

Abdelhamid, Emna; Figeac, Martin; Renneville, Aline; Quief, Sabine; Villenet, Céline; Boyer, Thomas D.; Nibourel, Olivier; Coiteux, Valérie; Cassinat, Bruno; Lippert, Éric; Hélevaut, Nathalie; Soua, Zohra; Preudhomme, Claude

doi:10.1002/ajh.23446

Cited by 9 publications

(5 citation statements)

References 4 publications

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“…To obtain very high coverage (i.e., approximately 2 million reads per sample), 24 samples were analyzed per run. Bioinformatic analysis was performed as described in our previous work [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

IDH1/2but notDNMT3Amutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the Acute Leukemia French Association

et al. 2015

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Acute myeloid leukemia (AML) is a heterogeneous disease. Even within the same NPM1-mutated genetic subgroup, some patients harbor additional mutations in FLT3, IDH1/2, DNMT3A or TET2. Recent studies have shown the prognostic significance of minimal residual disease (MRD) in AML but it remains to be determined which molecular markers are the most suitable for MRD monitoring. Recent advances in next-generation sequencing (NGS) have provided the opportunity to use multiple molecular markers. In this study, we used NGS technology to assess MRD in 31 AML patients enrolled in the ALFA-0701 trial and harboring NPM1 mutations associated to IDH1/2 or DNMT3A mutations. NPM1 mutation-based MRD monitoring was performed by RTqPCR. IDH1/2 and DNMT3A mutations were quantified by NGS using an Ion Torrent Proton instrument with high coverage (2 million reads per sample). The monitoringof IDH1/2 mutations showed that these mutations were reliable MRD markers that allowed the prediction of relapse in the majority of patients. Moreover, IDH1/2 mutation status predicted relapse or disease evolution in 100% of cases if we included the patient who developed myelodysplastic syndrome. In contrast, DNMT3A mutations were not correlated to the disease status, as we found that a preleukemic clone with DNMT3A mutation persisted in 40% of the patients who were in complete remission, reflecting the persistence of clonal hematopoiesis.

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Section: Methodsmentioning

confidence: 99%

IDH1/2but notDNMT3Amutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the Acute Leukemia French Association

et al. 2015

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“…In recent years, NGS has become more widely available and although these platforms may not currently be suited for the detection and/or quantitation of MPN‐associated mutations in all diagnostic laboratories, the feasibility and accuracy of these methods have already been established in MPN molecular diagnostics: targeted exome sequencing allows the identification of several mutations that have prognostic significance with identification of these mutations demonstrated to be of clinical value in predicting relapse in the post‐ASCT setting . With improvements in sensitivity, targeted NGS of specific MPN‐associated mutations may also afford the detection of residual disease and leukaemic transformation . Development and implementation of both commercial and in‐house NGS‐based assays for the detection of MPN‐associated mutations will require both inter‐ and intralaboratory evaluation of ongoing performance with preliminary studies addressing these issues achieving high concordance .…”

Section: Future Directionsmentioning

confidence: 99%

Molecular diagnostics of myeloproliferative neoplasms

Langabeer

Andrikovics

Asp

et al. 2015

European J of Haematology

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Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. Whilst many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN-associated mutations are considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN-associated mutations, and it therefore appears likely that emerging technologies such as next-generation sequencing and digital PCR will in the future play an increasing role in the molecular diagnosis of MPN.

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“…184,185,197 Abdelhamid et al demonstrated in a proof-of-principle study robust detection of JAK2 V617F in PB by HTS with high concordance to qPCR, even at low AFs. 199 Lundberg et al applied a targeted HTS panel (104 genes) to serial blood samples and showed that the number of emergent mutations over time was low, characterizing these diseases as genetically stable. This study also illustrated the capability of HTS to detect the expansion of preexisting clones harboring TP53 and TET2 mutations toward transformation to AML.…”

Section: Chronic Myeloid Leukemiamentioning

confidence: 99%

High-throughput sequencing for noninvasive disease detection in hematologic malignancies

Scherer

Kurtz

Diehn

et al. 2017

Blood

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Noninvasive monitoring of minimal residual disease (MRD) has led to significant advances in personalized management of patients with hematologic malignancies. Improved therapeutic options and prolonged survival have further increased the need for sensitive tumor assessment that can inform treatment decisions and patient outcomes. At diagnosis or relapse of most hematologic neoplasms, malignant cells are often easily accessible in the blood as circulating tumor cells (CTCs), making them ideal targets to noninvasively profile the molecular features of each patient. In other cancer types, CTCs are generally rare and noninvasive molecular detection relies on circulating tumor DNA (ctDNA) shed from tumor deposits into circulation. The ability to precisely detect and quantify CTCs and ctDNA could minimize invasive procedures and improve prediction of clinical outcomes. Technical advances in MRD detection methods in recent years have led to reduced costs and increased sensitivity, specificity, and applicability. Among currently available tests, high-throughput sequencing (HTS)–based approaches are increasingly attractive for noninvasive molecular testing. HTS-based methods can simultaneously identify multiple genetic markers with high sensitivity and specificity without individual optimization. In this review, we present an overview of techniques used for noninvasive molecular disease detection in selected myeloid and lymphoid neoplasms, with a focus on the current and future role of HTS-based assays.

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Quantification of JAK2V617F mutation by next‐generation sequencing technology

Cited by 9 publications

References 4 publications

IDH1/2but notDNMT3Amutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the Acute Leukemia French Association

IDH1/2but notDNMT3Amutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the Acute Leukemia French Association

Molecular diagnostics of myeloproliferative neoplasms

High-throughput sequencing for noninvasive disease detection in hematologic malignancies

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