rev bras hematol hemoter. 2015;37(2):71–72
w w w . r b h h . o r g
Revista
Brasileira
de
Hematologia
e
Hemoterapia
Brazilian
Journal
of
Hematology
and
Hemotherapy
Scientific
Comment
Metaphase
cytogenetics
and
single
nucleotide
polymorphism
arrays
in
myeloid
malignancies
夽
Fernanda
Borges
da
Silva,
Fabiola
Traina
∗UniversityofSãoPauloatRibeirãoPretoMedicalSchool,RibeirãoPreto,SP,Brazil
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Articlehistory:
Availableonline30January2015
Chromosomal abnormalities provide useful diagnostic and prognostic information, and may also guide therapy in myeloid malignancies, especially in myelodysplastic syn-dromes(MDS)andacutemyeloidleukemia(AML).Therevised internationalprognosticscoresystemforMDShighlightsthe implicationofchromosomalabnormalitiesontheprognosis of MDS patients.1 The successes of acute promyelocytic leukemia patients harboring t(15;17) and treated with all-transretinoicacid(ATRA)indicatesthevalueofchromosomal abnormalities on the diagnosis, prognosis and therapy of AML.2Metaphasecytogeneticsisaroutinetestinthe man-agementofmyeloidmalignanciesthatallowsthedetectionof multipleclones,unbalancedchromosomaldefects(deletions andgains)andbalancedtranslocations.However,metaphase cytogeneticsistimeconsuming,itneedscellularproliferation, itssensitivitydependsontheproportionofclonalcellsinthe sample,anditsresolutiondependsonthesizeofthelesion.At least50%ofMDSandAMLpatientshavenormalmetaphase cytogenetic results, and the great clinical diversity among thesepatientshasindicatedtheneedfornewtechniquesable todetectadditionalmolecularalterationsthatcanhelpinthe diagnosis,prognosisandtreatment.Wholegenomescanning technologieshaveopenedupanewroadofinvestigationfor chromosomal abnormalities in myeloid malignancies and also other neoplasms.3 Array-based technologies include
夽
SeepaperbyNoronhaetal.inRevBrasHematolHemoter.2015;37(1):48–54.
∗ Correspondingauthorat:DepartmentofInternalMedicine,FaculdadedeMedicinadeRibeirãoPreto(FMRP),UniversidadedeSãoPaulo
(USP),Av.Bandeirantes,3900,14049-900RibeirãoPreto,SP,Brazil. E-mailaddress:[email protected](F.Traina).
comparativegenomichybridizationarrays(CGH-A)andsingle nucleotidepolymorphismarrays(SNP-A).4Morerecently,next generation sequencing (NGS) technologyhas alsoprovided valuableinformationonchromosomalabnormalities.5
In the last issue ofthe Revista Brasileira de Hematolo-giaeHemoterapia,Noronhaetal.6reportedthecomparative results ofmetaphase cytogenetics and SNP-A in 25 Brazil-ian patientswith diagnoses ofAMLor MDS;chromosomal abnormalities weredetectedin40%and 68%ofpatientsby metaphasecytogeneticsandSNP-Atechnology,respectively. AsdemonstratedbyNoronhaetal.,6SNP-Atechnologydoes notdependon thepresenceofdividingcells,hasthe abil-ity todetect copy number variations (deletions and gains) withahigherresolutionthanconventionalcytogenetics,and to detect copy number neutralloss ofheterozygosity (CN-LOH),alsonamedsomaticuniparentaldisomy(UPD).However, SNP-Adoesnotdetectbalancedtranslocations,doesnot dis-tinguishindividualclones;anddoesnotdetectsmallclones.4 Assuch,SNP-Adoesnotreplacemetaphasecytogenetics,and combinedmethodswillprobablybenecessarytoimprovethe clinicalcareofpatientswithmyeloidmalignancies.Another interestingissueillustratedbyNoronhaetal.6wasthe com-parison ofSNP-Aresultsobtainedfromthe germ-line DNA sample (buccalcells)and the tumorsample (bonemarrow mononuclearcells).Thisapproachisrecommendedtoexclude
http://dx.doi.org/10.1016/j.bjhh.2015.01.007
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revbrashematolhemoter.2015;37(2):71–72normalcopynumbervariationsfromsomatic/acquiredgains, deletionsorUPD.Normalcopynumbervariations,ingeneral, aresmallerthan1Mbandmayhavecharacteristiclocations,7 asindicatedinpublicdatabases.
TwootherimportantcontributionsofSNP-Atechnologyto myeloidmalignanciesneedtobehighlighted.SNP-Awasfirst usedasaninvestigative tool,whichallowedthe identifica-tionofvariouscommondeletedregionsandthediscoveryof severalimportantgenemutationsexemplifiedbyCBL,TET2, and EZH2mutations.8 Newlesions detectedbySNP-Amay haveprognosticimplicationsinMDS9 andAML10;however, thevalidationofthisfindingindifferentcohortsofpatients isnecessary.ThehighcostofSNP-Alimitsitsuseinthe rou-tineclinicalsetting.TheworkbyNoronhaetal.6 represents animportantstepinestablishingtheuseofSNP-Ain Brazil-ianpatientswithmyeloidmalignanciesinaresearchscenario, whichmaybeimportanttobetterdefinethesomatic chromo-somalabnormalitiesinourpopulationandmaybeavaluable tooltoinvestigatemolecularmechanismsinvolvedin Brazil-iancasesoffamilialmyeloidmalignancies.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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