Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study.
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.
Coyaud
Etienne
E
Inserm, U563, 31024 Toulouse, France.
Struski
Stephanie
S
Prade
Nais
N
Familiades
Julien
J
Eichner
Ruth
R
Quelen
Cathy
C
Bousquet
Marina
M
Mugneret
Francine
F
Talmant
Pascaline
P
Pages
Marie-Pierre
MP
Lefebvre
Christine
C
Penther
Dominique
D
Lippert
Eric
E
Nadal
Nathalie
N
Taviaux
Sylvie
S
Poppe
Bruce
B
Luquet
Isabelle
I
Baranger
Laurence
L
Eclache
Virginie
V
Radford
Isabelle
I
Barin
Carole
C
Mozziconacci
Marie-Joëlle
MJ
Lafage-Pochitaloff
Marina
M
Antoine-Poirel
Hélène
H
Charrin
Christiane
C
Perot
Christine
C
Terre
Christine
C
Brousset
Pierre
P
Dastugue
Nicole
N
Broccardo
Cyril
C
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
D015514:Oncogene Proteins, Fusion; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human