False positivity of ETV6/RUNX1 detected by FISH in healthy newborns and adults

Pediatr Blood Cancer. 2014 Sep;61(9):1704-6. doi: 10.1002/pbc.25050. Epub 2014 Apr 17.

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).

Keywords: acute lymphoblastic leukemia; etiology; fluorescence in situ hybridization; natural history; specificity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant, Newborn
  • Oncogene Proteins, Fusion / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Prognosis
  • Translocation, Genetic / genetics*

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • TEL-AML1 fusion protein