Single-nucleotide polymorphism array (SNP-A) improves the identification of chromosomal abnormalities by metaphase cytogenetics in myelodysplastic syndrome.
OBJECTIVE
The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal haematopoietic stem cell disorders characterised by inefficient haematopoiesis and risk of progression to acute myeloid leukaemia. Metaphase cytogenetics is an extremely valuable clinical tool in the management of haematological malignancies. However, metaphase cytogenetics requires cellular proliferation, its sensitivity and resolution depends on the proportion of clonal cells in the sample and size of the lesion, respectively. Single-nucleotide polymorphism array (SNP-A) does not depend on the presence of dividing cells, is able to detect copy number variations with a high resolution and to detect copy number neutral loss of heterozygosity or uniparental disomy (UPD). The aim of this study was to illustrate that the use of SNP-A can cover cryptic chromosomal lesions not identified by metaphase cytogenetics in patients with MDS.


METHODS
Metaphase cytogenetics was performed on bone marrow aspirate using standard methods. Genomic DNA from total bone marrow cells were submitted to SNP-A using Affymetrix Genome-Wide Human SNP CytoScan HD.


RESULTS
In our cohort of 15 patients with a diagnosis of MDS and related diseases, chromosomal abnormalities were found in 47% of the cases by SNP-A and in 33% by metaphase cytogenetics. SNP-A detected all lesions identified by metaphase cytogenetics, except a balanced translocation and a marker chromosome. Notably, SNP-A detected a total of 30 new lesions: 1 (3%) gain, 17 (57%) losses and 12 (40%) UPDs in 5 patients with MDS.


CONCLUSIONS
SNP-A may complement metaphase cytogenetics to improve the detection of chromosomal abnormalities in myeloid neoplasms.
Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
Fernanda Borges
FB
da Silva
Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
João Agostinho
JA
Machado-Neto
Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
Virginia Helena Leira Lipoli
VHLL
Bertini
Cytogenetics Laboratory, Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil.|Department of Hematology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil.
Elvira Deolinda Rodrigues Pereira
EDRP
Velloso
Cytogenetics Laboratory, Hospital Israelita Albert Einstein, São Paulo, São Paulo, Brazil.
Cristina Alonso
CA
Ratis
Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
Rodrigo T
RT
Calado
Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
Belinda Pinto
BP
Simões
Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
Eduardo Magalhães
EM
Rego
Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
Fabiola
F
Traina
D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D002869:Chromosome Aberrations; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007621:Karyotyping; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D024182:Uniparental Disomy
CYTOGENETICS; LEUKAEMIA; MYELODYSPLASIA