Identification of TP53 as an acute lymphocytic leukemia susceptibility gene through exome sequencing

BC Powell, L Jiang, DM Muzny… - Pediatric blood & …, 2013 - Wiley Online Library
BC Powell, L Jiang, DM Muzny, LR Treviño, ZAE Dreyer, LC Strong, DA Wheeler, RA Gibbs…
Pediatric blood & cancer, 2013Wiley Online Library
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 …
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. Pediatr Blood Cancer 2013; 60: E1–E3. © 2012 Wiley Periodicals, Inc.
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