Abstract
The 11p15.5 chromosomal region contains one or more loci involved in congenital developmental abnormalities and in the genesis of embryonal tumors, such as Wilms' tumor, embryonal rhabdomyosarcoma, and hepatoblastoma. In these tumors, a loss of constitutive heterozygosity, selectively involving a specific parental allele, suggests both the presence of onco-suppressor genes and a phenomenon of genomic imprinting. We present evidence that both genetic events could be occasionally involved in hepatoblastoma. In fact, loss of heterozygosity at 11p15.5 could be documented in 3 of 13 patients with hepatoblastoma, and in 2 cases the paternal origin of the residual allele in the tumor was assessed. Moreover, imprinting of the paternal IGFII allele and the maternal H19 allele was confirmed in normal tissues of 5 informative patients. Finally, imprinting relaxation of IGFII was detected in the tumor tissue of 1 patient.
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Abbreviations
- IGFII:
-
insulin-like growth factor II
- BWS:
-
Beckwith-Wiedemann syndrome
- eRMS:
-
embryonal rhabdomyosarcoma
References
Barlow DP, Stoger R, Herrmann BG, Saito K, Schweifer N (1991) The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to theTme locus. Nature 349:84–87
Bartolomei MS, Zemel S, Tilghman SM (1991) Parental imprinting of the mouse H19 gene. Nature 351:153–155
Brannan CI, Dees EC, Ingram RS, Tilghman SM (1990) The product of the H19 gene may function as an RNA. Mol Cell Biol 10:28–36
Brown KW, Gardner A, Williams JC, Mott MG, McDermott, Maitland NJ (1992) Paternal origin of 11p15 duplications in the Beckwith-Wiedemann syndrome. Cancer Genet Cytogenet 58:66–70
Byrne JA, Simme LA, Little MH, Algar EM, Smith PJ (1993) Three non over-lapping regions of chromosome arm 11p allele loss identified in infantile tumours of adrenal and liver. Genes Chromosomes Cancer 8:104–111
DeChiara TM, Robertson EJ, Efstratiadis A (1991) Parental impringting of the mouse insulin-like growth factor II gene. Cell 64:849–859
Fearon ER, Feinberg AP, Hamilton SH, Vogelstein B (1985) Loss of genes on the short arm of chromosome 11 in bladder cancer. Nature 318:377–380
Ferguson-Smith AC, Cattanach BM, Barton SC, beechey CV, Surani MA (1991) Embryological and molecular investigation of parental imprinting on mouse chromosome 7. Nature 351:667–670
Goto J, Figlewicz DA, Marineau C, Khodr N, Rouleau GA (1992) Dinucleotide repeat polymorphism at the IGF2R locus. Nucleic Acids Res 20:923
Haas OA, Zoubek A, Grumayer ER, Gadner H (1986) Constitutional interstitial deletion of 11p11 and pericentric inversion of chromosome 9 in a patient with Beckwith-Wiedemann syndrome and hepatoblastoma. Cancer Genet Cytogenet 23:95–104
Hao Y, Crenshaw T, Moulton T, Newcomb E, Tycko B (1993) Tumour-suppressor activity of H19 RNA. Nature 365:764–767
Hayward NK, Little MH, Mortimer RH, Clouston WM, Smith PJ (1987) Generation of homozygosity at the c-Ha-ras-1 locus on chromosome 11p in an adrenal adenoma from an adult with Wiedemann-Beckwith syndrome. Cancer Genet Cytogenet 30:127–132
Henry I, Grandjounad S, Couillin P, Barichard F, Huerre-Jeanpierre C, Glaser T, Philip T, Lenoir G, Chaussain JL, Junien C (1989) Tumor specific loss of 11p15.5 alleles in del 11p13 Wilms' tumor and infamilial adrenocortical carcinomas. Proc Natl Acad Sci USA 86:3247–3251
Junien C, Heyningen V van (1991) Report of the committee on the genetic constitution of chromosome 11. Cytogenet Cell Genet 58:459–554
Kalscheuer VM, Mariman EC, Schepens MT, Rehder H, Ropers HH (1993) The insulin-like growth factor type-2 receptor gene is imprinted in the mouse but not in humans. Nature Genet 5:74–78
Koi M, Johnson LA, Kalikin LM, Little PFR, Nakamura Y, Feinberg AP (1993) Tumour cell growth arrest caused by subchromosomal transferable DNA fragments from chromosome 11. Science 260:361–364
Koufos A, Hansen MF, Copeland MG, Jenkins NA, Lampkin BC, Cavenee WK (1985) Loss of heterozygosity in three embrional tumours suggests a common pathogenetic mechanism. Nature 316:330–334
Koufos A, Grundy P, Morgan K, Aleck KA, Hadro T, Lampkin BC, Kalbakji A, Cavenee WK (1989) Familial Wiedemann-Beckwith syndrome and a second Wilms' tumour locus both map to 11p15.5. Am J Hum Genet 44:711–719
Little M, Thomsom DB, Hayward NK, Smith PJ (1988). Loss of alleles on the short arm of chromosome 11 in hepatoblastoma from a child with Beckwith-Wiedemann syndrome. Hum Genet 79:186–189
Mannens M, Slater RM, Heyting C, Bliek J, de-Kraker J, Coad N, de-Pagter-Holthuizen P, Pearson PL (1988) Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 11 in Wilms' tumours. Hum Genet 81:41–48
Neitzel H (1986) A routine method for the establishment of permanent growing lymphoblastoid cell lines. Hum Genet 73:320–326
Ogawa O, Eccles MR, Szeto J, McNoe LA, Yun K, Maw MA, Smith PJ, Reeve AE (1993a) Relaxation of insulin-like growth factor II gene imprinting in Wilms' tumour Nature 362:749–751
Ogawa O, Becroft DM, Morison IM, Eccles MR, Skeen JE, Mauger DC, Reeve AE (1993b) Constitutional relaxation of insulin-like growth factor II gene imprinting associated with Wilms' tumour and gigantism. Nature Genet 5:408–412
Pal N, Wadey, RB, Buckle B, Yeomans E, Pritchard J Cowell JK (1990) Preferential loss of maternal alleles in sporadic Wilms' tumor. Oncogene 5:1665–1668
Rainier S, Johnson LA, Dobry CJ, Ping AJ, Grundy PE, Feinberg AP (1993) Relaxation of imprinted genes in human cancer. Nature 362:747–749
Scrable H, Witte D, Shimada H, Seemayer, T, Wang-Wuu S, Soukup S, Koufos, A, Houghton P, Lamkin B, Cavenee W (1989a) Molecular differential pathology of rhabdomyosarcoma. Genes Chromosome Cancer 1:23–35
Scrable HJ, Cavenee W, Ghavimi F, Lovell M, Morgan K, Sapienza C (1989b) A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting. Proc Natl Acad Sci USA 86:7480–7484
Seizinger BR, Klinger HP, Junien P, Nakamura Y, Le Beau M, Cavenee W, Emmanuel B, Ponder B, Naylor S, Mitelman F, Louis D, Menon A, Newsham I, Deker J, Kaebling M, Henry I, Deimling A von (1991) Eleventh Workshop on Human Gene Mapping. Report of the committee on chromosome and gene loss in human neoplasia. Cytogenet Cell Genet 58:1080–1096
Weksberg R, Shen DR, Fei YL, Song QL, Squire J (1993) Disruption of insulin-like growth factor 2 imprinting in Beckwith-Wiedemann syndrome. Nature Genet 5:143–150
Wilkins RJ (1988) Genomic imprinting and carcinogenesis. Lancet i: 329–331
Zhang Y, Shields T, Crenshaw T, Hao Y, Moulton T, Tyco B (1993) Imprinting of human H19: allele-specific CpG methylation, loss of the active allele in Wilms' tumor, and potential for somatic allele switching. Am J Hum Genet 53:113–124
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Montagna, M., Menin, C., Chieco-Bianchi, L. et al. Occasional loss of constitutive heterozygosity at 11p15.5 and imprinting relaxation of theIGFII maternal allele in hepatoblastoma. J Cancer Res Clin Oncol 120, 732–736 (1994). https://doi.org/10.1007/BF01194272
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DOI: https://doi.org/10.1007/BF01194272