A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia

Shah S., Schrader K.A., Waanders E., Timms A.E., Vijai J., Miething C., Wechsler J., Yang J., Hayes J., Klein R.J., Zhang J., Wei L., Wu G., Rusch M., Nagahawatte P., Ma J., Chen S.-C., Song G., Cheng J., Meyers P., Bhojwani D., Jhanwar S., Maslak P., Fleisher M., Littman J., Offit L., Rau-Murthy R., Fleischut M.H., Corines M., Murali R., Gao X., Manschreck C., Kitzing T., Murty V.V., Raimondi S.C., Kuiper R.P., Simons A., Schiffman J.D., Onel K., Plon S.E., Wheeler D.A., Ritter D., Ziegler D.S., Tucker K., Sutton R., Chenevix-Trench G., Li J., Huntsman D.G., Hansford S., Senz J., Walsh T., Lee M., Hahn C.N., Roberts K.G., King M.-C., Lo S.M., Levine R.L., Viale A., Socci N.D., Nathanson K.L., Scott H.S., Daly M., Lipkin S.M., Lowe S.W., Downing J.R., Altshuler D., Sandlund J.T., Horwitz M.S., Mullighan C.G. and Offit K. (2013) A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia. Nature Genetics, 45 10: 1226-1231. doi:10.1038/ng.2754

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Author Shah S.
Schrader K.A.
Waanders E.
Timms A.E.
Vijai J.
Miething C.
Wechsler J.
Yang J.
Hayes J.
Klein R.J.
Zhang J.
Wei L.
Wu G.
Rusch M.
Nagahawatte P.
Ma J.
Chen S.-C.
Song G.
Cheng J.
Meyers P.
Bhojwani D.
Jhanwar S.
Maslak P.
Fleisher M.
Littman J.
Offit L.
Rau-Murthy R.
Fleischut M.H.
Corines M.
Murali R.
Gao X.
Manschreck C.
Kitzing T.
Murty V.V.
Raimondi S.C.
Kuiper R.P.
Simons A.
Schiffman J.D.
Onel K.
Plon S.E.
Wheeler D.A.
Ritter D.
Ziegler D.S.
Tucker K.
Sutton R.
Chenevix-Trench G.
Li J.
Huntsman D.G.
Hansford S.
Senz J.
Walsh T.
Lee M.
Hahn C.N.
Roberts K.G.
King M.-C.
Lo S.M.
Levine R.L.
Viale A.
Socci N.D.
Nathanson K.L.
Scott H.S.
Daly M.
Lipkin S.M.
Lowe S.W.
Downing J.R.
Altshuler D.
Sandlund J.T.
Horwitz M.S.
Mullighan C.G.
Offit K.
Title A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
Publication date 2013-01-01
Sub-type Article (original research)
DOI 10.1038/ng.2754
Volume 45
Issue 10
Start page 1226
End page 1231
Total pages 6
Publisher New York, NY, U.S.A.
Language eng
Subject 1311 Genetics
Abstract Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL), but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly183Ser), affecting the octapeptide domain of PAX5 that was found to segregate with disease in two unrelated kindreds with autosomal dominant B-ALL. Leukemic cells from all affected individuals in both families exhibited 9p deletion, with loss of heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional sporadic ALL cases with 9p loss harbored somatic PAX5 substitutions affecting Gly183. Functional and gene expression analysis of the PAX5 mutation demonstrated that it had significantly reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B cell ALL and implicate PAX5 in a new syndrome of susceptibility to pre-B cell neoplasia.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
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Created: Tue, 01 Apr 2014, 23:44:29 EST by Matthew Lamb on behalf of School of Medicine