ETV6-RUNX1 fusion gene and additional genetic changes in infant leukemia: a genome-wide analysis

Area of Science:

• Pediatric Oncology
• Cancer Genomics
• Hematology

Background:

• Infant acute lymphoblastic leukemia (ALL) commonly features MLL gene rearrangements.
• The ETV6-RUNX1 fusion gene is typically found in children over two years old.
• The presence of ETV6-RUNX1 in younger infants presents a unique opportunity to study leukemia development.

Purpose of the Study:

• To investigate the genomic landscape of infant ALL cases with the ETV6-RUNX1 fusion gene.
• To identify genetic alterations contributing to the early onset of leukemia in these rare cases.
• To compare copy number abnormalities between infant and older pediatric ALL patients with t(12;21).

Main Methods:

• Whole-genome copy number analysis using single-nucleotide polymorphism (SNP) arrays.
• Comparative analysis of genetic abnormalities in infant ETV6-RUNX1 positive ALL versus older pediatric ALL cohorts.
• Identification of recurrent deletions and patient-specific genomic alterations.

Main Results:

• Four infant cases (2-7 months) with the ETV6-RUNX1 fusion gene were identified.
• Recurrent deletions at 9p21.3, 11p13, and 12p13.2 were observed.
• No specific genetic abnormalities fully explained the rapid development of leukemia in infants, though copy number abnormalities increased with age.

Conclusions:

• Infant ETV6-RUNX1 positive ALL cases do not show unique genetic drivers for their early onset.
• The frequency of copy number abnormalities correlates with age in these patients.
• This study provides novel insights into the etiology of ETV6-RUNX1 positive ALL using SNP array analysis.