title: Clonal analysis of deletions on chromosome 20q and JAK2-V617F in MPD suggests that del20q acts independently and is not one of the predisposing mutations for JAK2-V617F.
abstract: We developed a real-time copy number polymerase chain reaction assay for deletions on chromosome 20q (del20q), screened peripheral blood granulocytes from 664 patients with myeloproliferative disorders, and identified 19 patients with del20q (2.9%), of which 14 (74%) were also positive for JAK2-V617F. To examine the temporal relationship between the occurrence of del20q and JAK2-V617F, we performed colony assays in methylcellulose, picked individual burst-forming units-erythroid (BFU-E) and colony-forming units-granulocyte (CFU-G) colonies, and genotyped each colony individually for del20q and JAK2-V617F. In 2 of 9 patients, we found that some colonies with del20q carried only wild-type JAK2, whereas other del20q colonies were JAK2-V617F positive, indicating that del20q occurred before the acquisition of JAK2-V617F. However, in colonies from 3 of 9 patients, we observed the opposite order of events. The lack of a strict temporal order of occurrence makes it doubtful that del20q represents a predisposing event for JAK2-V617F. In 2 patients with JAK2-V617F and 1 patient with MPL-W515L, microsatellite analysis revealed that del20q affected chromosomes of different parental origin and/or 9pLOH occurred at least twice. The fact that rare somatic events, such as del20q or 9pLOH, occurred more than once in subclones from the same patients suggests that the myeloproliferative disorder clone carries a predisposition to acquiring such genetic alterations.
authors.affiliation: Department of Biomedicine, Experimental Hematology, University Hospital Basel, Basel, Switzerland.
authors.forename: Franz X
authors.initials: FX
authors.lastname: Schaub
authors.forename: Roland
authors.initials: R
authors.lastname: Jäger
authors.forename: Renate
authors.initials: R
authors.lastname: Looser
authors.forename: Hui
authors.initials: H
authors.lastname: Hao-Shen
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hermouet
authors.forename: François
authors.initials: F
authors.lastname: Girodon
authors.forename: Andre
authors.initials: A
authors.lastname: Tichelli
authors.forename: Heinz
authors.initials: H
authors.lastname: Gisslinger
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
authors.forename: Radek C
authors.initials: RC
authors.lastname: Skoda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D002872:Chromosome Deletion; D002890:Chromosomes, Human, Pair 20 / Q000502:physiology; D002999:Clone Cells / Q000473:pathology; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology*; D010649:Phenylalanine / Q000235:genetics; D014633:Valine / Q000235:genetics
chemical_list: D010649:Phenylalanine; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D014633:Valine