Single-nucleotide polymorphism array (SNP-A) improves the identification of chromosomal abnormalities by metaphase cytogenetics in myelodysplastic syndrome

Silva, Fernanda Borges da; Machado-Neto, João Agostinho; Bertini, Virginia Helena Leira Lipoli; Velloso, Elvira Deolinda Rodrigues Pereira; Ratis, Cristina Alonso; Calado, Rodrigo T.; Simões, Belinda Pinto; Rego, Eduardo Magalhães; Traina, Fabı́ola

doi:10.1136/jclinpath-2016-204023

Cited by 18 publications

(15 citation statements)

References 31 publications

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“…On the other hand, DNA array-based methods, such as SNP arrays, increased the resolution up to the base-pair level, enabling studies of copy number variants (CNVs) and acquired UPD. CNVs are amplified or deleted regions ranging in size from intermediate (1-50 kb) to large and are recognized as a major source of human genome variability [Sebat et al, 2004;da Silva et al, 2016]. Importantly, CNVs are involved in cancer development and can increase during tumor progression, influencing phenotype and prognosis.…”

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confidence: 99%

High Frequency of Copy-Neutral Loss of Heterozygosity in Patients with Myelofibrosis

Paula

Nonino²,

Nascimento³

et al. 2018

Cytogenet Genome Res

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Myelofibrosis is the rarest and most severe type of Philadelphia-negative classical myeloproliferative neoplasms. Although mutually exclusive driver mutations in JAK2, MPL, or CALR that activate JAK-STAT pathway have been related to the pathogenesis of the disease, chromosome abnormalities have also been associated with the phenotype and prognosis of the disease. Here, we report the use of a chromosomal microarray platform consisting of both oligo and SNP probes to improve the detection of chromosome abnormalities in patients with myelofibrosis. Sixteen patients with myelofibrosis were tested, and the results were compared to karyotype analysis. Driver mutations in JAK2, MPL, or CALR were investigated by PCR and MLPA. Conventional cytogenetics revealed chromosome abnormalities in 3 out of 16 cases (18.7%), while chromosomal microarray analysis detected copy-number variations (CNV) or copy-neutral loss of heterozygosity (CN-LOH) alterations in 11 out of 16 (68.7%) patients. These included 43 CN-LOH, 14 deletions, 1 trisomy, and 1 duplication. Ten patients showed multiple chromosomal abnormalities, varying from 2 to 13 CNVs or CN-LOHs. Mutational status for JAK2, CALR, and MPL by MLPA revealed a total of 3/16 (18.7%) patients positive for the JAK2 V617F mutation, 9 with CALR deletion or insertion and 1 positive for MPL mutation. Considering that most of the CNVs identified were smaller than the karyotype resolution and the high frequency of CN-LOHs in our study, we propose that chromosomal microarray platforms that combine oligos and SNP should be used as a first-tier genetic test in patients with myelofibrosis.

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confidence: 99%

High Frequency of Copy-Neutral Loss of Heterozygosity in Patients with Myelofibrosis

Paula

Nonino²,

Nascimento³

et al. 2018

Cytogenet Genome Res

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“…When combined with cytogenic and molecular studies such as FISH and SNP arrays, detection of recurrent or unbalanced chromosomal aberrations improves to nearly 80% and such helps improve risk stratification and diagnostic accuracy. [83][84][85] In general, chromosomal loss such as deletion of the long arm of chromosome 5 (del(5q)) and del(7q) is more common than chromosomal gain like trisomy 8. Due to an increased understanding of their predictive value with regards to treatment response, prognosis and clinical outcomes, chromosomal abnormalities have been integrated into the IPSS.…”

Section: Y Tog Ene Tic Ab Normalitie Smentioning

confidence: 99%

The genetic and molecular pathogenesis of myelodysplastic syndromes

Shallis

Ahmad

Zeidan

2018

European J of Haematology

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Myelodysplastic syndromes (MDS) comprise a diverse group of clonal and malignant myeloid disorders characterized by ineffective hematopoiesis, resultant peripheral cytopenias, and a meaningful increased risk of progression to acute myeloid leuke- (WES) has enhanced this recognition and the detection of subtle irregularities that escape conventional karyotyping. As a direct result, the understanding of the molecular pathogenesis of MDS has expanded and influenced the use of prognostic metrics, management decisions, and future therapeutic endeavors. | S O M ATI C M UTATI O N SCellular pathways, including those involved in RNA splicing, DNA transcription, signal transduction, and epigenetic regulation, are

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“…Addition of FISH and high resolution single nucleotide polymorphism (SNP) array analyses can provide additional structural abnormality data allowing further reclassification. However, it should be noted that the IPSS-R used only metaphase karyotyping, and it is unclear whether the same clinical correlations will be apparent using higher resolution technology [47,48]. The most frequently occurring cytogenetic abnormality of del(5q) is found in~15% of patients with MDS [49].…”

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

Application of Genomics to Clinical Practice in Haematological Malignancy

et al. 2019

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Purpose of Review The usual abundance of fresh cells and high-quality DNA derived from bone marrow aspirate and peripheral blood mean haematological malignancies are at the forefront of the application of genomics to malignancy. This review evaluates where genomics is routinely used in clinical care and where opportunities for further application exist. Recent Findings The 2016 revision of the WHO classification of tumours of haematopoietic and lymphoid tissues increased the number of disease entities defined by, or whose diagnosis was strongly supported by, a specific genetic change. Increasingly combinations of mutations rather than individual lesions are being used to genomically classify heterogeneous disorders to inform prognosis and direct treatment. Furthermore, the role of different genetic aberrations as markers of measurable residual disease is being evaluated in clinical trials to allow intensification/de-intensification of treatment as appropriate and early detection of relapse. Summary Implementation of broader sequencing technologies such as whole exome/genome sequencing coupled with continuing developments in genomic technology to improve turnaround times are likely to further reinforce the centrality of genomics in the management of haematological malignancies.

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Single-nucleotide polymorphism array (SNP-A) improves the identification of chromosomal abnormalities by metaphase cytogenetics in myelodysplastic syndrome

Abstract: SNP-A may complement metaphase cytogenetics to improve the detection of chromosomal abnormalities in myeloid neoplasms.

Cited by 18 publications

References 31 publications

High Frequency of Copy-Neutral Loss of Heterozygosity in Patients with Myelofibrosis

High Frequency of Copy-Neutral Loss of Heterozygosity in Patients with Myelofibrosis

The genetic and molecular pathogenesis of myelodysplastic syndromes

Application of Genomics to Clinical Practice in Haematological Malignancy

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