title: RAS mutation is associated with hyperdiploidy and parental characteristics in pediatric acute lymphoblastic leukemia.
abstract: We explored the relationship of RAS gene mutations with epidemiologic and cytogenetic factors in a case series of children with leukemia. Diagnostic bone marrow samples from 191 incident leukemia cases from the Northern California Childhood Leukemia Study were typed for NRAS and KRAS codon 12 and 13 mutations. A total of 38 cases (20%) harbored RAS mutations. Among the 142 B-cell acute lymphoblastic leukemia (ALL) cases, RAS mutations were more common among Hispanic children (P=0.11) or children born to mothers <30 years (P=0.007). Those with hyperdiploidy at diagnosis (>50 chromosomes) had the highest rates of RAS mutation (P=0.02). A multivariable model confirmed the significant associations between RAS mutation and both maternal age and hyperdiploidy. Interestingly, smoking of the father in the 3 months prior to pregnancy was reported less frequently among hyperdiploid leukemia patients than among those without hyperdiploidy (P=0.02). The data suggest that RAS and high hyperdiploidy may be cooperative genetic events to produce the leukemia subtype; and furthermore, that maternal age and paternal preconception smoking or other factors associated with these parameters are critical in the etiology of subtypes of childhood leukemia.
authors.affiliation: Laboratory for Molecular Epidemiology, Department of Epidemiology and Biostatistics, and UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA. wiemels@itsa.ucsf.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Wiemels
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: S
authors.initials: S
authors.lastname: Zheng
authors.forename: C
authors.initials: C
authors.lastname: Metayer
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: M T
authors.initials: MT
authors.lastname: Smith
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.forename: S
authors.initials: S
authors.lastname: Selvin
authors.forename: P A
authors.initials: PA
authors.lastname: Buffler
authors.forename: J K
authors.initials: JK
authors.lastname: Wiencke
mesh_terms: D000293:Adolescent; D001856:Bone Marrow Examination; D002140:California / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D020732:Cytogenetic Analysis; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D018811:Maternal Exposure; D009154:Mutation; D018812:Paternal Exposure; D011123:Polyploidy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology; D044465:White People / Q000235:genetics