title: Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study.
abstract: PAX5 is the main target of somatic mutations in acute B lymphoblastic leukemia (B-ALL). We analyzed 153 adult and child B-ALL harboring karyotypic abnormalities at chromosome 9p, to determine the frequency and the nature of PAX5 alterations. We found PAX5 internal rearrangements in 21% of the cases. To isolate fusion partners, we used classic and innovative techniques (rolling circle amplification-rapid amplification of cDNA ends) and single nucleotide polymorphism-comparative genomic hybridization arrays. Recurrent and novel fusion partners were identified, including NCoR1, DACH2, GOLGA6, and TAOK1 genes showing the high variability of the partners. We noted that half the fusion genes can give rise to truncated PAX5 proteins. Furthermore, malignant cells carrying PAX5 fusion genes displayed a simple karyotype. These data strongly suggest that PAX5 fusion genes are early players in leukemogenesis. In addition, PAX5 deletion was observed in 60% of B-ALL with 9p alterations. Contrary to cases with PAX5 fusions, deletions were associated with complex karyotypes and common recurrent translocations. This supports the hypothesis of the secondary nature of the deletion. Our data shed more light on the high variability of PAX5 alterations in B-ALL. Therefore, it is probable that gene fusions occur early, whereas deletions should be regarded as a late/secondary event.
authors.affiliation: Inserm, U563, 31024 Toulouse, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Coyaud
authors.forename: Stephanie
authors.initials: S
authors.lastname: Struski
authors.forename: Nais
authors.initials: N
authors.lastname: Prade
authors.forename: Julien
authors.initials: J
authors.lastname: Familiades
authors.forename: Ruth
authors.initials: R
authors.lastname: Eichner
authors.forename: Cathy
authors.initials: C
authors.lastname: Quelen
authors.forename: Marina
authors.initials: M
authors.lastname: Bousquet
authors.forename: Francine
authors.initials: F
authors.lastname: Mugneret
authors.forename: Pascaline
authors.initials: P
authors.lastname: Talmant
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Pages
authors.forename: Christine
authors.initials: C
authors.lastname: Lefebvre
authors.forename: Dominique
authors.initials: D
authors.lastname: Penther
authors.forename: Eric
authors.initials: E
authors.lastname: Lippert
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nadal
authors.forename: Sylvie
authors.initials: S
authors.lastname: Taviaux
authors.forename: Bruce
authors.initials: B
authors.lastname: Poppe
authors.forename: Isabelle
authors.initials: I
authors.lastname: Luquet
authors.forename: Laurence
authors.initials: L
authors.lastname: Baranger
authors.forename: Virginie
authors.initials: V
authors.lastname: Eclache
authors.forename: Isabelle
authors.initials: I
authors.lastname: Radford
authors.forename: Carole
authors.initials: C
authors.lastname: Barin
authors.forename: Marie-Joëlle
authors.initials: MJ
authors.lastname: Mozziconacci
authors.forename: Marina
authors.initials: M
authors.lastname: Lafage-Pochitaloff
authors.forename: Hélène
authors.initials: H
authors.lastname: Antoine-Poirel
authors.forename: Christiane
authors.initials: C
authors.lastname: Charrin
authors.forename: Christine
authors.initials: C
authors.lastname: Perot
authors.forename: Christine
authors.initials: C
authors.lastname: Terre
authors.forename: Pierre
authors.initials: P
authors.lastname: Brousset
authors.forename: Nicole
authors.initials: N
authors.lastname: Dastugue
authors.forename: Cyril
authors.initials: C
authors.lastname: Broccardo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056905:Chromosome Breakpoints; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003001:Cloning, Molecular; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D005260:Female; D005602:France; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D051757:PAX5 Transcription Factor / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D015514:Oncogene Proteins, Fusion; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human