title: Identification of TP53 as an acute lymphocytic leukemia susceptibility gene through exome sequencing.
abstract: Although acute lymphocytic leukemia (ALL) is the most common childhood cancer, genetic predisposition to ALL remains poorly understood. Whole-exome sequencing was performed in an extended kindred in which five individuals had been diagnosed with leukemia. Analysis revealed a nonsense variant of TP53 which has been previously reported in families with sarcomas and other typical Li Fraumeni syndrome-associated cancers but never in a familial leukemia kindred. This unexpected finding enabled identification of an appropriate sibling bone marrow donor and illustrates that exome sequencing will reveal atypical clinical presentations of even well-studied genes.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Bradford C
authors.initials: BC
authors.lastname: Powell
authors.forename: Lichun
authors.initials: L
authors.lastname: Jiang
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Treviño
authors.forename: Zoann E
authors.initials: ZE
authors.lastname: Dreyer
authors.forename: Louise C
authors.initials: LC
authors.lastname: Strong
authors.forename: David A
authors.initials: DA
authors.lastname: Wheeler
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Plon
mesh_terms: D059472:Exome; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53