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Chromosome aberrations in mesoblastic nephroma
D E Schofield1, E J Yunis, J A Fletcher
1Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Abstract:
Mesoblastic nephroma (MN) is the most common renal tumor diagnosed in infancy. Histologically, MNs are designated as classic, cellular, or mixed type based upon variations in cellularity. Recent karyotypic reports have suggested that extra copies of chromosome 11 are a nonrandom occurrence in MNs. We analyzed nuclear suspensions prepared from a group of 17 formalin-fixed, paraffin-embedded tumors to determine the possible role of chromosome 11 copy number in the genesis of MN. Extra copies of D11Z1 (a probe for the centromeric region of chromosome 11) were detected in seven out of 10 MNs with cellular or mixed histology, whereas each of six classic histology MNs were disomic for D11Z1 (P < 0.05). Additional fluorescence in situ hybridization studies utilizing the probes for the alpha satellite, centromeric regions of chromosomes 7, 8, 9, 12, 17, and 20 were then carried out on all cases with cellular or mixed histology. Five out of 10 cellular or mixed MNs had extra copies of D8Z1, and four out of 10 had extra copies of D17Z1, suggesting that gains of chromosomes 8 and 17 may be additional nonrandom cytogenetic events associated with the evolution of MNs. DNA aneuploidy, as determined by image analysis, was detected in three tumors: all had greater than four chromosomal aberrations documented by fluorescence in situ hybridization.
Insights
Mesoblastic nephroma (MN), a common infant kidney tumor, shows extra copies of chromosome 11 in cellular and mixed types. Gains of chromosomes 8 and 17 also appear linked to MN development.
Area of Science:
- Pediatric Oncology
- Cytogenetics
- Molecular Pathology
Background:
- Mesoblastic nephroma (MN) is the most frequent renal tumor in infants.
- Histological subtypes include classic, cellular, and mixed, differentiated by cellularity.
- Previous studies suggested a potential link between extra chromosome 11 copies and MN.
Purpose of the Study:
- To investigate the role of chromosome copy number in the development of mesoblastic nephroma.
- To determine if extra copies of chromosome 11 are specifically associated with certain MN histological subtypes.
- To explore additional nonrandom cytogenetic events in cellular and mixed MN.
Main Methods:
- Analysis of nuclear suspensions from 17 formalin-fixed, paraffin-embedded MN tumors.
- Fluorescence in situ hybridization (FISH) using probes for chromosome 11 (D11Z1) and other chromosomes (7, 8, 9, 12, 17, 20).
- DNA aneuploidy assessment via image analysis.
Main Results:
- Extra copies of D11Z1 (chromosome 11) were found in 7/10 cellular or mixed MNs, but not in classic MNs (P < 0.05).
- Additional gains of D8Z1 (chromosome 8) and D17Z1 (chromosome 17) were observed in 5/10 and 4/10 cellular/mixed MNs, respectively.
- DNA aneuploidy was present in 3 tumors, all exhibiting more than four chromosomal aberrations by FISH.
Conclusions:
- Increased copy number of chromosome 11 is associated with cellular and mixed types of mesoblastic nephroma.
- Gains of chromosomes 8 and 17 represent potential nonrandom cytogenetic events in MN evolution.
- Cytogenetic analysis, including FISH, is crucial for understanding MN pathogenesis and potential progression markers.