Wilms' tumor with an apparently balanced translocation t(X;18) resulting in deletion of the WTX gene.
The recent description of a new X chromosome tumor suppressor gene, WTX, that is commonly inactivated in Wilms' tumor prompted us to examine the possible involvement of WTX in a case of Wilms' tumor containing an apparently balanced reciprocal translocation between chromosomes X and 18 (t(X;18)(q11;p11)). Fluorescence in situ hybridization (FISH) analysis of paraffin tumor sections indeed revealed a deletion of the WTX locus at Xq11. High-resolution array comparative genomic hybridization (array CGH) analysis of tumor DNA revealed a 1.5 Mb chromosome deletion encompassing the WTX gene at Xq11. No loss of genetic material was detected on chromosome 18. Interestingly, unlike most tumors with acquired chromosomal translocations, where a new fusion oncogene or promoter-oncogene fusion is created and drives tumor growth, the t(X;18) in this tumor appears to drive tumorigenesis via deletion of a tumor suppressor. This case demonstrates the importance of array CGH and FISH as adjuncts in tumor cytogenetics and in identifying pathogenic microdeletions in "balanced" translocations that are not truly balanced.
Han
Moonjoo
M
Molecular Diagnostics Laboratory, Department of Pathology, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA.
Rivera
Miguel N
MN
Batten
Julie M
JM
Haber
Daniel A
DA
Dal Cin
Paola
P
Iafrate
A John
AJ
D048868:Adaptor Proteins, Signal Transducing; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics* / Q000378:metabolism
C517118:AMER1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D025521:Tumor Suppressor Proteins