title: Duplication of the paternal IGF2 allele in trisomy 11 and elevated expression levels of IGF2 mRNA in congenital mesoblastic nephroma of the cellular or mixed type.
abstract: In a metaphase comparative genomic hybridization and fluorescence in situ hybridization study of 13 congenital mesoblastic nephroma (CMN) tumors, trisomy 11 was found in seven cellular or mixed type tumors, disomy 11 with other chromosome changes in two cellular type tumors, and no chromosome changes in four classical type tumors. Reverse-transcription (RT)-PCR analysis detected the ETV6-NTRK3 fusion transcript in all eight cellular or mixed type tumors examined, but not in four classical type tumors. All seven tumors with trisomy 11 showed duplication of the paternal IGF2 allele, and six cellular or classical type tumors with disomy 11 showed one paternal and one maternal allele of IGF2, analyzing the methylation status of the sixth CTCF site of the H19-differentially methylated region. Allelic expression study using the ApaI/AvaII polymorphism site at exon 9 of IGF2 showed retention of imprinting in all seven tumors examined. Quantitative real-time RT-PCR analysis showed higher expression levels of IGF2 mRNA in three of three cellular type tumors with trisomy 11, in one cellular type tumor with disomy 11, and in three of four classical tumors than in fetal kidneys or normal kidney tissues. Thus, duplicated paternal IGF2 resulted in elevated IGF2 mRNA levels, and may provide CMN or its precursor cells with a proliferative advantage. The mechanism explaining that some cellular or classical type tumors with disomy 11 also showed elevated IGF2 mRNA levels remains unresolved. IGF2 clearly plays an important role in the tumorigenic process of CMN, although it is difficult to assess its exact role.
authors.affiliation: Department of Cancer Diagnosis, Research Institute for Clinical Oncology, Saitama Cancer Center, Ina, Saitama, and Department of Pediatrics, Juntendo University, Nerima Hospital, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Haruta
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Soejima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fukushi
authors.forename: Kinji
authors.initials: K
authors.lastname: Yokomori
authors.forename: Hisaya
authors.initials: H
authors.lastname: Nakadate
authors.forename: Hajime
authors.initials: H
authors.lastname: Okita
authors.forename: Jun-ich
authors.initials: JI
authors.lastname: Hata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuzawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kaneko
mesh_terms: D000483:Alleles; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D018392:Genomic Imprinting; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007680:Kidney Neoplasms / Q000151:congenital / Q000235:genetics / Q000378:metabolism; D008297:Male; D018201:Nephroma, Mesoblastic / Q000151:congenital / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic; D014314:Trisomy; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D007335:Insulin-Like Growth Factor II; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C484319:ETV6-NTRK3 fusion protein, human; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein