High-resolution molecular cytogenetic analysis of Wilms tumors highlights diagnostic difficulties among small round cell kidney tumors.
Many solid tumors exhibit characteristic gene fusions, which are reflected by balanced translocations at the cytogenetic level. These changes might be useful diagnostic and prognostic tools. In Wilms tumor (WT, nephroblastoma) no fusions genes or recurrent balanced translocations have been described thus far. To screen for cryptic balanced translocations, we have analyzed 17 renal neoplasms, histopathologically classified as WT, by a combination of G-banding, multicolor FISH, and subtelomeric FISH. This approach revealed several submicroscopic chromosomal aberrations and three different seemingly balanced translocations, resulting in a heterozygous deletion of HACE1, an EWSR1/ERG fusion, and an EWSR1/FLI1 fusion, respectively. As EWSR1 rearrangements are known to be a characteristic of Ewing tumors (ET), our findings illustrate the diagnostic problems regarding small cell kidney tumors and strongly argue for the need of adjuvant diagnostic techniques in this group of neoplasms. In summary, our genomic screening approach proved efficient in finding structural chromosomal aberrations. The fact that no recurrent translocations were found in the WTs of this study argues against the presence of a frequent pathognomonic translocation in this disease entity.
Stewénius
Ylva
Y
Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. ylva.stewenius@med.lu.se
Jin
Yuesheng
Y
Ora
Ingrid
I
Panagopoulos
Ioannis
I
Möller
Emely
E
Mertens
Fredrik
F
Sandstedt
Bengt
B
Alumets
Jan
J
Akerman
Måns
M
Merks
Johannes Hm
JH
de Kraker
Jan
J
Gisselsson
David
D
D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002877:Chromosomes, Human / Q000235:genetics; D003937:Diagnosis, Differential; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D051789:Proto-Oncogene Protein c-fli-1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D034802:RNA-Binding Protein EWS; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016615:Telomere / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology
C450460:EWS-ERG fusion protein, human; C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors; C497506:HACE1 protein, human; D044767:Ubiquitin-Protein Ligases