title: TP53Mutations in Hypodiploid Acute Lymphoblastic Leukemia.
abstract: Acute lymphoblastic leukemia (ALL) is an aggressive neoplasm of B- or T-lymphoid progenitors and is the commonest childhood tumor. ALL comprises multiple subtypes characterized by distinct genetic alterations, with stereotyped patterns of aneuploidy present in many cases. Although alterations ofTP53are common in many tumors, they are infrequent in ALL, with the exception of two ALL subtypes associated with poor outcome: relapsed disease and ALL with hypodiploidy.TP53alterations are present in almost all cases of ALL with low hypodiploidy and are associated with alterations of the lymphoid transcription factorIKZF2and the tumor-suppressor gene lociCDKN2AandCDKN2B.Remarkably, more than half ofTP53mutations in low-hypodiploid ALL in children are present in nontumor cells, indicating that low-hypodiploid ALL is a manifestation of Li-Fraumeni syndrome. These findings have profound implications for our understanding of the genetic pathogenesis of hypodiploid ALL, suggesting that alteration of TP53 function may promote the distinctive aneuploidy characteristic of hypodiploid ALL. Moreover, the identification of hypodiploidy mandates offering testing forTP53mutational status to patients and their relatives, with appropriate counseling and disease surveillance.
authors.affiliation: Departments of Pathology and the Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Evan Q
authors.initials: EQ
authors.lastname: Comeaux
authors.affiliation: Departments of Pathology and the Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Mullighan
mesh_terms: D000782:Aneuploidy; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53