A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia (original) (raw)

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Acknowledgements

We thank M.A.S. Moore and S. Jae-Hung for their contributions to ongoing tumor studies (Sloan-Kettering Institute); G. Dressler (University of Michigan) for the mouse GRG4 construct; M. Busslinger (The Research Institute for Molecular Pathology) for the luc-CD19 reporter construct; J. Hagman (National Jewish) for providing a PAX5 vector and the J558LμM cell line; D. Payne-Turner (St. Jude Children's Research Hospital) for technical assistance; W. Yang and C. Smith (Pharmaceutical Sciences, St. Jude Children's Research Hospital) for their assistance in the haplotype analyses; and the Tissue Resources Core Facility, Pediatric Cancer Genome Project Core Facility and Flow Cytometry and Cell Sorting Core Facility of St. Jude Children's Research Hospital. We thank the families for their generous participation in these studies. This project was supported by grant I5-A523 from the Starr Cancer Consortium, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Sabin Family Research Fund, the Lymphoma Foundation, Geoffrey Beene Cancer Research Center grant 78730, the Sharon Levine Corzine Foundation, the Barbara L. Goldsmith Genetics Research Fund, Cancer Prevention and Research Institute of Texas grant RP101089, the New South Wales Priory of the Knights of the Order of Saint John, the Matthew Bell Foundation, National Cancer Institute of the US National Institutes of Health (NIH) Comprehensive Cancer Center Core grant CA21765, the American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital and grant R01DK58161 from the US NIH. R.P.K. is funded by a grant from the Dutch Cancer Society (KUN2009-4298). T.K. is supported by a German Research Foundation Postdoctoral Fellowship (KI1605/1-1). C.G.M. is a Pew Scholar in the Biomedical Sciences and a St. Baldrick's Scholar. K.G.R. is supported by a National Health and Medical Research Council (NHMRC, Australia) CJ Martin Postdoctoral Fellowship. K.A.S. is funded by the Canadian Institutes of Health Research. A.E.T. is supported by T32GM007454 from the National Institute of General Medical Sciences (NIGMS). G.C.-T. is a Senior Principal Research Fellow of the NHMRC. E.W. is funded by the Dutch Cancer Society, project number KUN2012-5366. H.S.S. is a Principal Research Fellow of the NHMRC (APP1023059), and the work was supported by grant APP1024215.

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Author notes

1. Sohela Shah, Kasmintan A Schrader, Esmé Waanders, Andrew E Timms, Joseph Vijai and Cornelius Miething: These authors contributed equally to this work.
2. John T Sandlund, Marshall S Horwitz, Charles G Mullighan and Kenneth Offit: These authors jointly directed this work.

Authors and Affiliations

1. Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
   Sohela Shah, Kasmintan A Schrader, Joseph Vijai, Cornelius Miething, James Hayes, Robert J Klein, Xiaoni Gao, Thomas Kitzing, Scott W Lowe & Kenneth Offit
2. Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
   Sohela Shah, Kasmintan A Schrader, Joseph Vijai, Robert J Klein, Jason Littman, Lily Offit, Rohini Rau-Murthy, Megan Harlan Fleischut, Marina Corines, Christopher Manschreck & Kenneth Offit
3. Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
   Esmé Waanders, Lei Wei, Jing Ma, Shann-Ching Chen, Guangchun Song, Jinjun Cheng, Susana C Raimondi, Kathryn G Roberts, James R Downing & Charles G Mullighan
4. Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences and Radboud Institute for Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands
   Esmé Waanders, Roland P Kuiper & Annet Simons
5. Department of Pathology, University of Washington, Seattle, Washington, USA
   Andrew E Timms, Jeremy Wechsler & Marshall S Horwitz
6. Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
   Jun Yang
7. Department of Computational Biology and Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
   Jinghui Zhang, Lei Wei, Gang Wu, Michael Rusch & Panduka Nagahawatte
8. Pediatric Cancer Genome Project Laboratory, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
   Jinjun Cheng
9. Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
   Paul Meyers
10. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
    Deepa Bhojwani & John T Sandlund
11. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    Suresh Jhanwar & Rajmohan Murali
12. Hematology Laboratory Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    Peter Maslak
13. Clinical Chemistry Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    Martin Fleisher
14. Department of Pathology and Cell Biology, Columbia University, New York, New York, USA
    Vundavalli V Murty
15. High-Risk Pediatric Cancer Clinic, Huntsman Cancer Institute/Primary Children's Medical Center, University of Utah, Salt Lake City, Utah, USA
    Joshua D Schiffman
16. Department of Pediatrics, University of Chicago, Chicago, Illinois, USA
    Kenan Onel
17. Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA
    Sharon E Plon, David A Wheeler & Deborah Ritter
18. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA
    Sharon E Plon, David A Wheeler & Deborah Ritter
19. Kids Cancer Centre, Sydney Children's Hospital, Sydney, New South Wales, Australia
    David S Ziegler
20. Children's Cancer Institute Australia for Medical Research, University of New South Wales, Randwick, New South Wales, Australia
    David S Ziegler & Rosemary Sutton
21. Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, New South Wales, Australia
    Kathy Tucker
22. Cancer Genetics Laboratory, The Queensland Institute of Medical Research, Herston, Queensland, Australia
    Georgia Chenevix-Trench & Jun Li
23. Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    David G Huntsman, Samantha Hansford & Janine Senz
24. Department of Medicine, University of Washington, Seattle, Washington, USA
    Tom Walsh, Ming Lee & Mary-Claire King
25. Department of Genome Sciences, University of Washington, Seattle, Washington, USA
    Tom Walsh, Ming Lee & Mary-Claire King
26. Department of Molecular Pathology, SA Pathology and Centre for Cancer Biology, Adelaide, South Australia, Australia
    Christopher N Hahn & Hamish S Scott
27. Department of Pediatrics, Weill Cornell College of Medicine, New York, New York, USA
    Sarah M Lo
28. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    Ross L Levine
29. Genomics Core Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    Agnes Viale
30. Bioinformatics Core, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    Nicholas D Socci
31. Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Katherine L Nathanson
32. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
    Mark Daly & David Altshuler
33. Department of Medicine, Weill Cornell College of Medicine, New York, New York, USA
    Steven M Lipkin & Kenneth Offit

Authors

1. Sohela Shah
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2. Kasmintan A Schrader
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3. Esmé Waanders
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4. Andrew E Timms
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5. Joseph Vijai
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6. Cornelius Miething
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7. Jeremy Wechsler
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8. Jun Yang
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9. James Hayes
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10. Robert J Klein
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11. Jinghui Zhang
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12. Lei Wei
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13. Gang Wu
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14. Michael Rusch
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15. Panduka Nagahawatte
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16. Jing Ma
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17. Shann-Ching Chen
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18. Guangchun Song
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19. Jinjun Cheng
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20. Paul Meyers
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21. Deepa Bhojwani
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22. Suresh Jhanwar
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23. Peter Maslak
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24. Martin Fleisher
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25. Jason Littman
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26. Lily Offit
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27. Rohini Rau-Murthy
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28. Megan Harlan Fleischut
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29. Marina Corines
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30. Rajmohan Murali
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31. Xiaoni Gao
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32. Christopher Manschreck
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33. Thomas Kitzing
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34. Vundavalli V Murty
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35. Susana C Raimondi
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36. Roland P Kuiper
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37. Annet Simons
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38. Joshua D Schiffman
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39. Kenan Onel
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40. Sharon E Plon
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41. David A Wheeler
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42. Deborah Ritter
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43. David S Ziegler
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44. Kathy Tucker
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45. Rosemary Sutton
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46. Georgia Chenevix-Trench
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47. Jun Li
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48. David G Huntsman
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49. Samantha Hansford
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50. Janine Senz
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51. Tom Walsh
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52. Ming Lee
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53. Christopher N Hahn
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54. Kathryn G Roberts
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55. Mary-Claire King
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56. Sarah M Lo
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57. Ross L Levine
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58. Agnes Viale
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59. Nicholas D Socci
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60. Katherine L Nathanson
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61. Hamish S Scott
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62. Mark Daly
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63. Steven M Lipkin
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64. Scott W Lowe
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65. James R Downing
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66. David Altshuler
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67. John T Sandlund
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68. Marshall S Horwitz
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69. Charles G Mullighan
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70. Kenneth Offit
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Contributions

K. Offit, C.G.M., M.S.H., J.T.S., S.S., K.A.S., E.W., A.E.T., J.V., C. Miething, S.M. Lipkin, R.J.K., M.D., D.A. and S.W.L. conceived and designed the experiment. S.S., K.A.S., E.W., A.E.T., J.V., C. Miething, J.W., J.Y., X.G., C. Manschreck, R.J.K., A.V., N.D.S., D.A., M.S.H., C.G.M., K. Offit, M.-C.K., T.W., M.L., T.K., D.B., J. Littman, L.O., S.C.R., P. Maslak, M.F., K.G.R. and J.C. performed the experiments. S.S., K.A.S., E.W., A.E.T., J.V., C. Miething, J.W., J.Y., R.J.K., N.D.S., M.S.H., C.G.M., K. Offit, L.W., J.Z., G.W., M.R., P.N., J.M., S.-C.C., G.S. and J.C. performed statistical analysis. S.S., K.A.S., E.W., A.E.T., J.V., C. Miething, J.W., J.Y., C. Manschreck, R.R.-M., M.C., R.M., M.H.F., S.M. Lipkin, R.J.K., A.V., N.D.S., D.A., C.N.H., H.S.S., S.W.L., M.S.H., C.G.M., K. Offit, L.W., J.H., J.Z., G.W., M.R., P.N., J.M., S.-C.C., G.S. and J.C. analyzed the data. E.W., C. Miething, J.T.S., S.J., M.H.F., J.S., V.V.M., S.E.P., D.G.H., D.S.Z., G.C.-T., S.M. Lipkin, S.M. Lo, R.L.L., A.V., K.L.N., M.D., D.A., C.N.H., H.S.S., S.W.L., M.S.H., C.G.M., K. Onel, R.P.K., A.S., J. Li, K.T., R.S., S.H., J.D.S., D.A.W., D.R., P. Meyers, J.Z., G.W., J.M., S.-C.C., J.R.D. and K. Offit contributed reagents, materials and analysis tools. K. Offit, C.G.M., M.S.H., S.S., K.A.S., E.W., A.E.T., J.V., C. Miething, J.Y., R.J.K. and S.W.L. wrote the manuscript. K. Offit, C.G.M., M.S.H., J.T.S., R.J.K., M.D., D.A. and S.W.L. jointly supervised the research.

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Correspondence toMarshall S Horwitz, Charles G Mullighan or Kenneth Offit.

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Shah, S., Schrader, K., Waanders, E. et al. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia.Nat Genet 45, 1226–1231 (2013). https://doi.org/10.1038/ng.2754

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• Received: 26 March 2013
• Accepted: 09 August 2013
• Published: 08 September 2013
• Issue Date: October 2013
• DOI: https://doi.org/10.1038/ng.2754