title: Prenatal origin of TEL-AML1-positive acute lymphoblastic leukemia in children born in California.
abstract: Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer. The peak incidence of ALL between ages 2 and 5 is accounted for by one subtype, referred to as common acute lymphoblastic leukemia (cALL). About 25% of cALL patients have the TEL-AML1 gene fusion derived from the t(12;21) chromosomal translocation. Recent evidence from retrospective analysis of neonatal blood spots (Guthrie cards) in Europe has demonstrated that this chromosome translocation may arise prenatally. The aim of our study was to determine whether TEL-AML1 fusions arise prenatally in a U.S. population of cALL patients. TEL-AML1-positive cALL cases (n = 14) were identified by fluorescence in situ hybridization, and the genomic breakpoints were identified by a streamlined long-distance PCR approach and sequenced. Clonotypic primers were designed for each patient breakpoint, and a nested PCR assay was used to determine the presence of the TEL-AML1 fusion sequence in neonatal Guthrie cards. Seven of 14 cases demonstrated clonotypic sequences on the archival Guthrie cards. The oldest patient that was positive was 6.7 years old at the time of diagnosis of leukemia. These results confirm previously published findings of a prenatal origin of TEL-AML1 in Europe by demonstrating its occurrence in a California-born population. Secondary changes were also similar to those described previously, with deletion of the second TEL allele being the most common. Other secondary changes included duplication of the fusion gene, trisomy 21, and monosomy X.
authors.affiliation: School of Public Health, University of California, Berkeley 94720-7360, USA.
authors.forename: Cliona M
authors.initials: CM
authors.lastname: McHale
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Wiemels
authors.forename: Luoping
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Ma
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Buffler
authors.forename: Weihong
authors.initials: W
authors.lastname: Guo
authors.forename: Mignon L
authors.initials: ML
authors.lastname: Loh
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Smith
mesh_terms: D002140:California / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000379:methods; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D011247:Pregnancy; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein