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Association of 11q loss, trisomy 12, and possible 16q loss with loss of imprinting of insulin‐like growth factor–II in Wilms tumor
Author(s) -
Watanabe Naoki,
Nakadate Hisaya,
Haruta Masayuki,
Sugawara Waka,
Sasaki Fumiaki,
Tsunematsu Yukiko,
Kikuta Atsushi,
Fukuzawa Masahiro,
Okita Hajime,
Hata Junichi,
Soejima Hidenobu,
Kaneko Yasuhiko
Publication year - 2006
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20321
Subject(s) - loss of heterozygosity , wilms' tumor , genomic imprinting , biology , haploinsufficiency , imprinting (psychology) , insulin like growth factor 2 , cancer research , ctcf , genetics , gene , allele , phenotype , enhancer , transcription factor , dna methylation , gene expression
Abstract We evaluated the WT1 and IGF2 status and performed chromosome and/or comparative genomic hybridization analysis in 43 tumor samples from patients with Wilms tumor. On this basis, we classified them into 4 groups: WT1 abnormality, loss of heterozygosity (LOH) of IGF2 , loss of imprinting (LOI) of IGF2 , and retention of imprinting (ROI) of IGF2, which were seen in 12%, 30%, 16%, and 42% of the tumors, respectively. Patients in the LOI group were older than those in other groups ( P < 0.01), and tumors in the WT1 group had fewer cytogenetic changes than did those in the other groups ( P < 0.01). It was found that 11q− and +12 were more frequent in the LOI group than in the WT1 +LOH+ROI group ( P < 0.01 and P < 0.01). There was no difference in the incidence of 16q− between the LOI group and the other groups; however, when we excluded 16 tumors with LOH on 11p15, 16q− tended to be more frequent in the LOI group than in the WT1 +ROI group ( P = 0.06). The association of 11q− or +12 with LOI of IGF2 found in the present study suggests that many tumors with no WT1 abnormalities need overexpression of IGF2 together with biallelic inactivation of the tumor‐suppressor gene on 11q and/or overexpression of growth‐promoting genes on chromosome 12. The 11q gene may code for one of the proteins that constitute a CTCF insulator complex, and its mutation, deletion, or haploinsufficiency may cause insulator abnormalities that might lead to LOI of IGF2 . © 2006 Wiley‐Liss, Inc.