Chromosome arm 16q in Wilms tumors: unbalanced chromosomal translocations, loss of heterozygosity, and assessment of the CTCF gene.
Chromosome arm 16q is a common site of loss of heterozygosity (LOH) in Wilms tumors (WTs). The mechanism and consequences of 16q LOH are not known, but the CTCF gene, in band 16q22, is a candidate target gene. CTCF protein binds to DNA upstream of the H19 gene on chromosome band 11p15, and maintains normal imprinting of H19 and IGF2. Thus, its loss might predispose to de novo methylation of the maternal allele of H19 and loss of imprinting (LOI) of IGF2 in WTs. We mapped Chr16 LOH in WTs and correlated this with unbalanced chromosomal translocations and histopathology. We also analyzed the CTCF gene for its mRNA and protein expression and DNA sequence, and we investigated correlations with methylation of H19(mat). In our series, unbalanced t(1;16) chromosomal translocations were a major pathway for Chr16 loss of heterozygosity, and this LOH was correlated significantly with tumor anaplasia. CTCF mapped in the minimal region of Chr16 LOH. However, we found no correlation between Chr16 LOH, or loss of CTCF mRNA or protein, and methylation of H19(mat). Some WTs contained reduced amounts of CTCF protein, but among these were cases with and without H19(mat) methylation. Rare WTs with simultaneous 16q LOH and H19(mat) methylation lacked CTCF mutations. These data argue against the CTCF gene as a target of Chr16 LOH in WTs, but leave open the possibility that post-transcriptional loss of CTCF protein may account for some instances of LOI.
Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Albert
A
Yeh
Michelle
M
Wei
Samuel B
SB
Golub
Darrell J
DJ
Yamashiro
Vundavali V
VV
Murty
Benjamin
B
Tycko
D000076246:CCCTC-Binding Factor; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D006801:Humans; D007621:Karyotyping; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics*
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors