| Literature DB >> 24013638 |
Sohela Shah1,2, Kasmintan A Schrader1,2, Esmé Waanders3,4, Andrew E Timms5, Joseph Vijai1,2, Cornelius Miething1, John T Sandlund6, Marshall S Horwitz5, Charles G Mullighan3, Kenneth Offit1,2, Jeremy Wechsler5, Jun Yang7, James Hayes1, Robert J Klein1,2, Jinghui Zhang8, Lei Wei8,3, Gang Wu8, Michael Rusch8, Panduka Nagahawatte8, Jing Ma9, Shann-Ching Chen3, Guangchun Song3, Jinjun Cheng3,9, Paul Meyers10, Deepa Bhojwani6, Suresh Jhanwar11, Peter Maslak12, Martin Fleisher13, Jason Littman2, Lily Offit2, Rohini Rau-Murthy2, Megan Harlan Fleischut2, Marina Corines2, Rajmohan Murali11, Xiaoni Gao1, Christopher Manschreck2, Thomas Kitzing1, Vundavalli V Murty14, Susana Raimondi3, Roland P Kuiper4, Annet Simons4, Joshua D Schiffman15, Kenan Onel16, Sharon E Plon17, David Wheeler17, Deborah Ritter17, David S Ziegler18, Kathy Tucker19, Rosemary Sutton20, Georgia Chenevix-Trench21, Jun Li21, David G Huntsman22, Samantha Hansford22, Janine Senz22, Thomas Walsh23, Ming Lee23, Christopher N Hahn24, Kathryn Roberts3, Mary-Claire King23, Sarah M Lo25, Ross L Levine26, Agnes Viale27, Nicholas D Socci28, Katherine L Nathanson29, Hamish S Scott24, Mark Daly30, Steven M Lipkin31, Scott W Lowe1, James R Downing3, David Altshuler30.
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.Entities:
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Year: 2013 PMID： 24013638 PMCID： PMC3919799 DOI： 10.1038/ng.2754
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330