title: False positivity of ETV6/RUNX1 detected by FISH in healthy newborns and adults.
abstract: The leukemia-associated ETV6-RUNX1-translocation frequently emerges prenatally. Reverse-transcriptase PCR screening may indicate presence of ETV6-RUNX1 transcripts in random cord blood samples. Subsequent cell enrichment validation finds significantly lower levels than validation applying fluorescence in situ hybridization (FISH) (<10(-5) vs. 10(-3) to 10(-4)). Using three FISH probe sets, we screened 179,000 cells from ETV6-RUNX1-positive dilution series, healthy adults and random cord blood samples. The t(12;21) single fusion extra signal translocation probe and the ETV6 break apart probe gave false positive results mimicking ETV6-RUNX1-positive cell levels of 10(-3). This questions the paradigm that 1% of newborns have ETV6-RUNX1-positive cells at levels of 10(-3) to 10(-4).
authors.affiliation: Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Maria Schioldan
authors.initials: MS
authors.lastname: Kusk
authors.forename: Ulrik
authors.initials: U
authors.lastname: Lausten-Thomsen
authors.forename: Mette Klarskov
authors.initials: MK
authors.lastname: Andersen
authors.forename: Marianne
authors.initials: M
authors.lastname: Olsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjalgrim
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
mesh_terms: D000328:Adult; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D014178:Translocation, Genetic / Q000235:genetics*; 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
keywords: acute lymphoblastic leukemia; etiology; fluorescence in situ hybridization; natural history; specificity