Mutational profiling in patients with MDS: Ready for every-day use in the clinic?

Bacher, Ulrike; Kohlmann, Alexander; Haferlach, Torsten

doi:10.1016/j.beha.2014.11.005

Cited by 26 publications

(15 citation statements)

References 43 publications

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“…Secondly, a number of articles (9, 6 %) focus generally on genetic or inherited disorders, which may or may not be rare diseases. Thirdly, some articles cover many possible diseases – such as cancer [ 42 , 43 ] or rare diseases [ 44 , 45 ] in general - while others focus specifically on one disease [ 46 – 48 ]. A significant number of articles (42, 29 %) did not focus on any diseases in particular, but addressed the impact of WES on all clinical contexts.…”

Section: Resultsmentioning

confidence: 99%

Unsolved challenges of clinical whole-exome sequencing: a systematic literature review of end-users’ views

2016

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BackgroundWhole-exome sequencing (WES) consists in the capture, sequencing and analysis of all exons in the human genome. Originally developed in the research context, this technology is now increasingly used clinically to inform patient care. The implementation of WES into healthcare poses significant organizational, regulatory, and ethical hurdles, which are widely discussed in the literature.MethodsIn order to inform future policy decisions on the integration of WES into standard clinical practice, we performed a systematic literature review to identify the most important challenges directly reported by technology users.ResultsOut of 2094 articles, we selected and analyzed 147 which reported a total of 23 different challenges linked to the production, analysis, reporting and sharing of patients’ WES data. Interpretation of variants of unknown significance, incidental findings, and the cost and reimbursement of WES-based tests were the most reported challenges across all articles.ConclusionsWES is already used in the clinical setting, and may soon be considered the standard of care for specific medical conditions. Yet, technology users are calling for certain standards and guidelines to be published before this technology replaces more focused approaches such as gene panels sequencing. In addition, a number of infrastructural adjustments will have to be made for clinics to store, process and analyze the amounts of data produced by WES.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-016-0213-6) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Unsolved challenges of clinical whole-exome sequencing: a systematic literature review of end-users’ views

2016

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“…Sample integrity was verified using standard NGS criteria (≥50 ng/μL, and OD 260/280:1.8‐2.0). We used a custom targeted NGS approach that combined multiplex PCR‐based target enrichment and library generation with ultra‐deep high‐throughput parallel sequencing using the Ion Proton Platform or MiSeq . A total of 15‐MDS‐relevant genes, including TET2, SF3B1, U2AF1, ASXL1, SRSF2, DNMT3A, RUNX1, EZH2, JAK2, NRAS, TP53, CBL, ETV6, IDH1, and IDH2, were covered, and exons with coding regions known to be hotspots or related with MDS (average depth >800 X) were targeted.…”

Section: Methodsmentioning

confidence: 99%

Mutation status and burden can improve prognostic prediction of patients with lower‐risk myelodysplastic syndromes

et al. 2019

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Patients with lower-risk myelodysplastic syndromes (LR-MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter-individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS-relevant genes in 159 patients with LR-MDS using nextgeneration sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129-4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 (P < .001; HR = 4.306, 95% CI: 2.144-8.650), TP53 (P = .004; HR = 4.863, 95% CI: 1.662-14.230)and JAK2 (P = .002; HR = 5.466, 95%CI: 1.848-16.169), as well as adjusted TET2 VAF ≥18% (P = .008; HR = 2.492, 95% CI: 1.273-4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR-MDS patients into three prognostically different groups (P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher-risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS-relevant genes may improve the prognostication of patients with LR-MDS and could help identify those with worse-than-expected prognosis for more aggressive treatment. K E Y W O R D Slower-risk myelodysplastic syndromes, mutation burden, mutation status, prognosis, variant allele frequency | 581 JIANG et Al.

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“…S većom dostupnosti ove metode i razvojem personalizirane medicine klasična citogenetika mogla bi postati manje bitna u MDS-u. 24…”

Section: Citogenetika Kao čImbenik Rizika U Mds-uunclassified

Prognostic Factors in Myelodysplastic Syndromes: Single-Center Experience

Milunović

Rogulj

Perica

et al. 2019

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Introduction: Myelodysplastic syndrome (MDS) is one of the most common myeloid neoplasms of elderly characterized by cytopenias and limited therapeutic options. The main aim of this retrospective single-center study was to examine the value of classical prognostic factors. The main outcome of the study was overall survival (OS) defined as death from MDS or any other reason. Methods: We analyzed the medical records of patients diagnosed with MDS at single centre in the period from beginning of 2013 to the end of 2016. Results: Total of 58 patients (median age of diagnosis being 69 years) were included in the study. After median of follow-up of 12 months, median OS was 17 months and estimated 3-year OS rate 25%. Classical prognostic systems such as IPSS, WPSS and R-IPSS were statistically significant prognostic factors discriminating adequately between low and high risk groups in terms of outcome. However, due to small sample size, we were not able to distinguish the most appropriate scoring system. The cytogenetics subgroups according to IPPS and R-IPSS were significant predictors of outcomes underlying its crucial role in MDS diagnosis. Despite the statistical tendency morphological features of MDS (2008 World Health Organization subtype and number of blasts in bone marrow) were not significant predictors of OS. Among clinical features, only presence and degree of anemia and transfusion dependency were significant predictors of inferior survival. Conclusion: The majority of traditional prognostic factors were significant in our cohort in concordance with literature review.

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Mutational profiling in patients with MDS: Ready for every-day use in the clinic?

Cited by 26 publications

References 43 publications

Unsolved challenges of clinical whole-exome sequencing: a systematic literature review of end-users’ views

Unsolved challenges of clinical whole-exome sequencing: a systematic literature review of end-users’ views

Mutation status and burden can improve prognostic prediction of patients with lower‐risk myelodysplastic syndromes

Prognostic Factors in Myelodysplastic Syndromes: Single-Center Experience

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