Perilobar nephrogenic rests and chromosome 22
Reena Mdzin1, Marianne Phillips, Caitlin Edwards
1School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.
Summary
Monosomy 22, a key genetic change in Wilms tumor (WT), occurs during the progression from precursor lesions called perilobar nephrogenic rests (NR) to WT. This loss of chromosome 22 is detected at varying rates in different NR subtypes.
Area of Science:
- Pediatric oncology
- Cancer genetics
- Developmental biology
Background:
- Perilobar nephrogenic rests (NR) are recognized precursor lesions for Wilms tumor (WT).
- Both NR and WT can exhibit similar genetic alterations, including chromosomal abnormalities.
- Understanding the timing of these genetic changes during tumor progression is crucial for comprehending WT development.
Observation:
- Two patients with WT, both presenting with perilobar NR, were analyzed.
- WT in both patients predominantly showed monosomy 22, while constitutional cytogenetics were normal.
- The study utilized fluorescent in situ hybridization (FISH) and microsatellite analysis to pinpoint the occurrence of monosomy 22.
Findings:
- Monosomy 22 rates increased with NR morphologic progression: approximately 30% in sclerotic/dormant NR to 50% in hyperplastic/adenomatous NR.
- WT exhibited a higher rate of monosomy 22, present in 60%-80% of nuclei.
- Microsatellite analysis confirmed loss of heterozygosity, with preferential loss of the same chromosome 22 allele in WT.
Implications:
- The findings suggest that loss of chromosome 22 occurs during the transition from perilobar NR to WT in a subset of cases.
- This study provides insights into the stepwise genetic evolution of Wilms tumor.
- Identifying the stage at which monosomy 22 is acquired can aid in understanding WT pathogenesis and potentially inform future diagnostic or therapeutic strategies.
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