European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms: reponse to the comments from the Francophone Group of Hematological Cytogenetics (GFCH)

Rack, KA; Berg, Eva van den; Haferlach, Claudia; Beverloo, H. Berna; Costa, Dolors; Espinet, Blanca; Foot, Nicola; Jeffries, Sally; Martin, Kristy-Jane; O’Connor, Sheila J.M.; Schoumans, Jacqueline; Talley, Polly; Telford, Nick; Stioui, Sabine; Zemanová, Zuzana; Hastings, Ros

doi:10.1038/s41375-020-0736-x

Cited by 12 publications

(13 citation statements)

References 3 publications

(4 reference statements)

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“…In adult AML, lack of cytogenetic information (karyotype and subsequent FISH/molecular analyses not performed at diagnosis or karyotype failure) could impair the outcome of these patients because they could not benefit from a risk-adapted therapy [155]. The proposed workflow for pediatric AML at diagnosis (Graphical Abstract) summarizes the laboratory practice according to the most recent recommendations [1,[31][32][33]38] and to the current risk-adapted therapeutic trials such as the French-U.K. MyeChild 01 trial (https://clinicaltrials.gov/ct2/show/NCT02724163) accessed on 4 June 2021.…”

Section: Cytogenetics Versus Molecular Analysismentioning

confidence: 99%

“…Cytogenetic analysis complemented by FISH (see graphical abstract) continues to play an important role in the diagnosis of AML, providing a rapid, global genome analysis, using FISH for the detection of cryptic chromosomal rearrangements, such as t(5;11)(q35;p15)/ NUP98-NSD1 [ 29 , 30 , 31 , 32 , 33 ]. In addition, classical chromosomal rearrangements can appear as variant “masked” forms, involving a third chromosome or as a cryptic insertion, requiring confirmation by FISH [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Quessada

Cuccuini

Saultier

et al. 2021

Genes

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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.

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Section: Cytogenetics Versus Molecular Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Quessada

Cuccuini

Saultier

et al. 2021

Genes

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“…Although there were no cytogenetic data available, we have used SNP array data to define genomic complexity. In none of the patients a high genomic complexity was indicated (Table 2), defined as 5 or more unbalanced aberrations according to Leeksma et al (47)(48)(49). Only two patients (1C and 3C) presented with three or four aberrations (Supplementary Table 4).…”

Section: Cll Families Show Similar Genomic Profilesmentioning

confidence: 99%

Consistent B Cell Receptor Immunoglobulin Features Between Siblings in Familial Chronic Lymphocytic Leukemia

et al. 2021

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Key processes in the onset and evolution of chronic lymphocytic leukemia (CLL) are thought to include chronic (antigenic) activation of mature B cells through the B cell receptor (BcR), signals from the microenvironment, and acquisition of genetic alterations. Here we describe three families in which two or more siblings were affected by CLL. We investigated whether there are immunogenetic similarities in the leukemia-specific immunoglobulin heavy (IGH) and light (IGL/IGK) chain gene rearrangements of the siblings in each family. Furthermore, we performed array analysis to study if similarities in CLL-associated chromosomal aberrations are present within each family and screened for somatic mutations using paired tumor/normal whole-genome sequencing (WGS). In two families a consistent IGHV gene mutational status (one IGHV-unmutated, one IGHV-mutated) was observed. Intriguingly, the third family with four affected siblings was characterized by usage of the lambda IGLV3-21 gene, with the hallmark R110 mutation of the recently described clinically aggressive IGLV3-21R110 subset. In this family, the CLL-specific rearrangements in two siblings could be assigned to either stereotyped subset #2 or the immunogenetically related subset #169, both of which belong to the broader IGLV3-21R110 subgroup. Consistent patterns of cytogenetic aberrations were encountered in all three families. Furthermore, the CLL clones carried somatic mutations previously associated with IGHV mutational status, cytogenetic aberrations and stereotyped subsets, respectively. From these findings, we conclude that similarities in immunogenetic characteristics in familial CLL, in combination with genetic aberrations acquired, point towards shared underlying mechanisms behind CLL development within each family.

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“…Note that there were no patients with retinoblastoma (5) in our cohort. The solid group is composed of all other primary cancer groups (6)(7)(8)(9)(10)(11)(12).…”

Section: Diagnostic Processmentioning

confidence: 99%

“…Also many leukemias have characteristic driver fusions [4]. Detection of these fusions for diagnostic purposes is usually done with targeted assays, which are reliable, fast and cost-effective, but limited to known partner genes and/or breakpoints [5,6]. As a result, targeted assays fail to detect some fusions with alternative breakpoints (e.g.…”

Section: Introductionmentioning

confidence: 99%

Systematic discovery of gene fusions in pediatric cancer by integrating RNA-seq and WGS

Belzen

Dan

Tuil

et al. 2021

Preprint

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Background Gene fusions are important cancer drivers in pediatric cancer and their accurate detection is essential for diagnosis and treatment. Clinical decision-making requires high confidence and precision of detection. Recent developments show RNA sequencing (RNA-seq) is promising for genome-wide detection of fusion products, but hindered by many false positives that require extensive manual curation and impede discovery of pathogenic fusions. Results We developed Fusion-sq to detect tumor-specific gene fusions by integrating and 'fusing' evidence from RNA-seq and whole genome sequencing (WGS) using intron-exon gene structure. In a pediatric pan-cancer cohort of 130 patients, we identified 165 high confidence tumor-specific gene fusions and their underlying structural variants (SVs). This includes all clinically relevant fusions known to be present in this cohort (30 patients). Fusion-sq distinguishes healthy-occurring from tumor-specific fusions, and resolves fusions in amplified regions and copy number unstable genomes. A high gene fusion burden is associated with copy number instability. We identified 27 potentially pathogenic fusions involving oncogenes or tumor-suppressor genes characterised by underlying SVs or expression changes indicative of activating or disruptive effects. Conclusions Our results indicate how clinically relevant and potentially pathogenic gene fusions can be identified and their functional effects investigated by combining WGS and RNA-seq. Integrating RNA fusion predictions with underlying SVs advances fusion detection beyond extensive manual filtering. Taken together, we developed a method for identifying candidate fusions that is suitable for precision oncology applications. Our method provides multi-omics evidence for assessing the pathogenicity of tumor-specific fusions for future clinical decision making.

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European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms: reponse to the comments from the Francophone Group of Hematological Cytogenetics (GFCH)

Cited by 12 publications

References 3 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

Consistent B Cell Receptor Immunoglobulin Features Between Siblings in Familial Chronic Lymphocytic Leukemia

Systematic discovery of gene fusions in pediatric cancer by integrating RNA-seq and WGS

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