Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers

Duncavage, Eric J.; Schroeder, Molly C.; O'Laughlin, Michele; Wilson, Roxanne; MacMillan, Sandra; Bohannon, A.S.; Kruchowski, Scott; Garza, John Carlos; Du, Feiyu; Hughes, Andrew; Robinson, Josh; Hughes, Emma; Heath, Sharon E.; Baty, Jack; Neidich, Julie; Christopher, Matthew; Jacoby, Meagan A.; Uy, Brian; Fulton, Robert S.; Miller, Christopher A.; Payton, Jacqueline E.; Link, Daniel C.; Walter, Matthew J.; Westervelt, Peter; DiPersio, John F.; Ley, Timothy J.; Spencer, David H.

doi:10.1056/nejmoa2024534

Cited by 198 publications

(184 citation statements)

References 24 publications

Supporting

Mentioning

163

Contrasting

Unclassified

Order By: Relevance

“…New technologies such as whole genome sequencing (WGS) could replace such workflows in the future, as suggested in a recent cost/effect comparative adult AML study [ 156 ]. However, a very high rate of unsuccessful karyotypes was observed in this study (especially if we include karyotypes with no abnormalities and fewer than 20 metaphases analyzed), much higher than the 4% pediatric and adult AML rate observed in the French report of quality indicators (C. Lefebvre and B. Gaillard for the GFCH, manuscript in preparation), the 2–7% rate reported in adult AML [ 130 , 155 ], or the 3–7% range reported in pediatric AML [ 22 , 157 ].…”

Section: Cytogenetics Versus Molecular Analysismentioning

confidence: 99%

Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge

Quessada

Cuccuini

Saultier

et al. 2021

Genes

View full text Add to dashboard Cite

Pediatric acute myeloid leukemia is a rare and heterogeneous disease in relation to morphology, immunophenotyping, germline and somatic cytogenetic and genetic abnormalities. Over recent decades, outcomes have greatly improved, although survival rates remain around 70% and the relapse rate is high, at around 30%. Cytogenetics is an important factor for diagnosis and indication of prognosis. The main cytogenetic abnormalities are referenced in the current WHO classification of acute myeloid leukemia, where there is an indication for risk-adapted therapy. The aim of this article is to provide an updated review of cytogenetics in pediatric AML, describing well-known WHO entities, as well as new subgroups and germline mutations with therapeutic implications. We describe the main chromosomal abnormalities, their frequency according to age and AML subtypes, and their prognostic relevance within current therapeutic protocols. We focus on de novo AML and on cytogenetic diagnosis, including the practical difficulties encountered, based on the most recent hematological and cytogenetic recommendations.

show abstract

Section: Cytogenetics Versus Molecular Analysismentioning

confidence: 99%

Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge

Quessada

Cuccuini

Saultier

et al. 2021

Genes

View full text Add to dashboard Cite

show abstract

“…Notably, six gene fusions not reported in the cytogenetic data were detected by WGS in NK-AML. This highlights the relevance of genomic sequencing to be implemented as clinical cytogenomic analyses as recently suggested [ 27 , 28 ]. Certain cryptic cytogenetic events of prognostic importance are difficult to capture in routine cytogenetic examinations, including, for instance, inv(16)(p13q24) ( CBFA2T3 - GLIS2 ) [ 29 ] and rearrangements involving 11p15 ( NUP98 fusions) [ 10 ].…”

Section: Discussionmentioning

confidence: 69%

“…Certain cryptic cytogenetic events of prognostic importance are difficult to capture in routine cytogenetic examinations, including, for instance, inv(16)(p13q24) ( CBFA2T3 - GLIS2 ) [ 29 ] and rearrangements involving 11p15 ( NUP98 fusions) [ 10 ]. For these cryptic events, WGS or transcriptome (RNA) sequencing may have a higher diagnostic yield detecting gene fusions or their expressed fusion transcripts, respectively [ 27 , 28 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML Cohort

Herlin

Yones

Kjeldsen

et al. 2021

Genes

View full text Add to dashboard Cite

Normal karyotype acute myeloid leukemia (NK-AML) constitutes 20–25% of pediatric AML and detailed molecular analysis is essential to unravel the genetic background of this group. Using publicly available sequencing data from the TARGET-AML initiative, we investigated the mutational landscape of NK-AML in comparison with abnormal karyotype AML (AK-AML). In 164 (97.6%) of 168 independent NK-AML samples, at least one somatic protein-coding mutation was identified using whole-genome or targeted capture sequencing. We identified a unique mutational landscape of NK-AML characterized by a higher prevalence of mutated CEBPA, FLT3, GATA2, NPM1, PTPN11, TET2, and WT1 and a lower prevalence of mutated KIT, KRAS, and NRAS compared with AK-AML. Mutated CEBPA often co-occurred with mutated GATA2, whereas mutated FLT3 co-occurred with mutated WT1 and NPM1. In multivariate regression analysis, we identified younger age, WBC count ≥50 × 109/L, FLT3-internal tandem duplications, and mutated WT1 as independent predictors of adverse prognosis and mutated NPM1 and GATA2 as independent predictors of favorable prognosis in NK-AML. In conclusion, NK-AML in children is characterized by a unique mutational landscape which impacts the disease outcome.

show abstract

“…However, NGS, which includes a variety of methods, is increasingly applied for cytogenetic analyses [ 10 , 31 ]. It already supplements conventional cytogenetic approaches and has the potential to replace them in certain applications in the future [ 32 ]. The evaluation of the largest GTR category “Molecular Genetics” would have exceeded the scope of this review.…”

Section: Resultsmentioning

confidence: 99%

Cytogenetic and Biochemical Genetic Techniques for Personalized Drug Therapy in Europe

2021

View full text Add to dashboard Cite

For many authorized drugs, accumulating scientific evidence supports testing for predictive biomarkers to apply personalized therapy and support preventive measures regarding adverse drug reactions and treatment failure. Here, we review cytogenetic and biochemical genetic testing methods that are available to guide therapy with drugs centrally approved in the European Union (EU). We identified several methods and combinations of techniques registered in the Genetic Testing Registry (GTR), which can be used to guide therapy with drugs for which pharmacogenomic-related information is provided in the European public assessment reports. Although this registry provides information on genetic tests offered worldwide, we identified limitations regarding standard techniques applied in clinical practice and the information on test validity rarely provided in the according sections.

show abstract

Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers

Cited by 198 publications

References 24 publications

Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge

Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge

What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML Cohort

Cytogenetic and Biochemical Genetic Techniques for Personalized Drug Therapy in Europe

Contact Info

Product

Resources

About