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Mutational and expression analysis of the chromosome 12p candidate tumor suppressor genes in pre-B acute lymphoblastic leukemia

Leukemia volume 18, pages 1499–1504 (2004)Cite this article

Abstract

Allelic losses on chromosome 12p12-13 are associated with childhood acute lymphoblastic leukemia (ALL) and several solid neoplasias, suggesting the presence of a tumor suppressor locus. The recent construction of a transcription map of this locus has enabled the identification of eight genes, of which five were previously known: ETV6, BCL-G, LRP6, MKP-7, and CDKN1B. The three other candidate genes, LOH12CR1, LOH12CR2, and LOH12CR3, have no known functions. To evaluate whether one (or more) of the candidate genes is the actual target of the 12p12-13 deletions, we examined the genomics and the expression status of these genes in ALL patients. Although we found nine DNA variants in these genes, no inactivating mutations were found in the leukemia cells of patients with 12p hemizygous deletions. Expression analysis revealed that most 12p hemizygously deleted samples also carried a t(12;21) translocation, of which none expressed ETV6 from the nontranslocated allele. Furthermore, we observed one case of t(12;21) without deletion of ETV6, in which the expression of this gene was greatly reduced, indicating a different mechanism of inactivation. None of the other genes showed a significant decrease in expression, suggesting that ETV6 is indeed the target of deletions in ALL patients.

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Acknowledgements

This work was supported by the Canadian Institutes of Health Research CIHR (grant number MOP-14108). DS is a scholar of the Fonds de la Recherche en Santé du Québec (FRSQ). AM and GB received studentships from the CIHR and the FRSQ, respectively.

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Authors and Affiliations

  1. Division of Hematology-Oncology, Research Center, Sainte-Justine Hospital, Montreal, Canada

    A Montpetit, J Larose, G Boily, S Langlois, N Trudel & D Sinnett

  2. Department of Biochemistry, University of Montreal, Montreal, Canada

    A Montpetit & D Sinnett

  3. Department of Pediatrics, University of Montreal, Montreal, Canada

    D Sinnett

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  1. A Montpetit
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  2. J Larose
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  3. G Boily
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  6. D Sinnett
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Correspondence to D Sinnett.

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Montpetit, A., Larose, J., Boily, G. et al. Mutational and expression analysis of the chromosome 12p candidate tumor suppressor genes in pre-B acute lymphoblastic leukemia. Leukemia 18, 1499–1504 (2004). https://doi.org/10.1038/sj.leu.2403441

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