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Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogénétique Hématologique study

(2010) BLOOD. 115(15). p.3089-3097
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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.
Keywords
MIGRATION, REPRESSION, CHROMOSOMES, TRANSLOCATIONS, CELLS, FUSION GENES, ACUTE LYMPHOBLASTIC-LEUKEMIA, TRANSCRIPTION FACTOR PAX5, CLONING, CANCER

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Chicago
Coyaud, Etienne, Stephanie Struski, Nais Prade, Julien Familiades, Ruth Eichner, Cathy Quelen, Marina Bousquet, et al. 2010. “Wide Diversity of PAX5 Alterations in B-ALL: a Groupe Francophone De Cytogénétique Hématologique Study.” Blood 115 (15): 3089–3097.
APA
Coyaud, E., Struski, S., Prade, N., Familiades, J., Eichner, R., Quelen, C., Bousquet, M., et al. (2010). Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogénétique Hématologique study. BLOOD, 115(15), 3089–3097.
Vancouver
1.
Coyaud E, Struski S, Prade N, Familiades J, Eichner R, Quelen C, et al. Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogénétique Hématologique study. BLOOD. 2010;115(15):3089–97.
MLA
Coyaud, Etienne, Stephanie Struski, Nais Prade, et al. “Wide Diversity of PAX5 Alterations in B-ALL: a Groupe Francophone De Cytogénétique Hématologique Study.” BLOOD 115.15 (2010): 3089–3097. Print.
@article{1066520,
  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.},
  author       = {Coyaud, Etienne and Struski, Stephanie and Prade, Nais and Familiades, Julien and Eichner, Ruth and Quelen, Cathy and Bousquet, Marina and Mugneret, Francine and Talmant, Pascaline and Pages, Marie-Pierre and Lefebvre, Christine and Penther, Dominique and Lippert, Eric and Nadal, Nathalie and Taviaux, Sylvie and Poppe, Bruce and Luquet, Isabelle and Baranger, Laurence and Eclache, Virginie and Radford, Isabelle and Barin, Carole and Mozziconacci, Marie-Jo{\"e}lle and Lafage-Pochitaloff, Marina and Antoine-Poirel, H{\'e}l{\`e}ne and Charrin, Christiane and Perot, Christine and Terre, Christine and Brousset, Pierre and Dastugue, Nicole and Broccardo, Cyril},
  issn         = {0006-4971},
  journal      = {BLOOD},
  keyword      = {MIGRATION,REPRESSION,CHROMOSOMES,TRANSLOCATIONS,CELLS,FUSION GENES,ACUTE LYMPHOBLASTIC-LEUKEMIA,TRANSCRIPTION FACTOR PAX5,CLONING,CANCER},
  language     = {eng},
  number       = {15},
  pages        = {3089--3097},
  title        = {Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytog{\'e}n{\'e}tique H{\'e}matologique study},
  url          = {http://dx.doi.org/10.1182/blood-2009-07-234229},
  volume       = {115},
  year         = {2010},
}

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