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Loss of heterozygosity in spontaneous and x-ray-induced intestinal tumors arising in F1 hybridMin mice: Evidence for sequential loss ofApc+ andDpc4 in tumor development

2000; Wiley; Volume: 28; Issue: 4 Linguagem: Inglês

10.1002/1098-2264(200008)28

1098-2264

Jackie Haines, Rosemary Dunford, J. D. Moody, M. Ellender, Roger Cox, Andrew Silver,

Cancer-related Molecular Pathways

Genes, Chromosomes and CancerVolume 28, Issue 4 p. 387-394 Research Article Loss of heterozygosity in spontaneous and x-ray–induced intestinal tumors arising in F1 hybrid Min mice: Evidence for sequential loss of Apc+ and Dpc4 in tumor development† Jackie Haines, Jackie Haines Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire, EnglandSearch for more papers by this authorRosemary Dunford, Rosemary Dunford Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire, EnglandSearch for more papers by this authorJohn Moody, John Moody Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire, EnglandSearch for more papers by this authorMichele Ellender, Michele Ellender Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire, EnglandSearch for more papers by this authorRoger Cox, Roger Cox Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire, EnglandSearch for more papers by this authorAndrew Silver, Corresponding Author Andrew Silver andy.silver@nrpb.org.uk Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire, EnglandNational Radiological Protection Board, Chilton, Oxfordshire, OX11 ORQ, EnglandSearch for more papers by this author Jackie Haines, Jackie Haines Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire, EnglandSearch for more papers by this authorRosemary Dunford, Rosemary Dunford Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire, EnglandSearch for more papers by this authorJohn Moody, John Moody Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire, EnglandSearch for more papers by this authorMichele Ellender, Michele Ellender Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire, EnglandSearch for more papers by this authorRoger Cox, Roger Cox Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire, EnglandSearch for more papers by this authorAndrew Silver, Corresponding Author Andrew Silver andy.silver@nrpb.org.uk Radiation Effects Department, National Radiological Protection Board, Chilton, Oxfordshire, EnglandNational Radiological Protection Board, Chilton, Oxfordshire, OX11 ORQ, EnglandSearch for more papers by this author First published: 14 June 2000 https://doi.org/10.1002/1098-2264(200008)28:4 3.0.CO;2-HCitations: 20 † Crown copyright 2000. Reproduced with the permission of the Conroller of Her Majesty's Stationary Office. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Min (multiple intestinal neoplasia) mice carry a mutant allele of the murine Apc (adenomatous polyposis coli) locus and are predisposed to intestinal adenoma formation in the intestinal tract. Early studies have shown complete loss of function of Apc by whole chromosome loss on the tumor-sensitive C57BL/6J genetic background and in AKR × B6 F1 hybrids. Gamma-radiation–induced chromosomal losses focus the critical region on wt Apc, but because of the limited number of polymorphic markers used, no other critical regions of loss on chromosome 18 were identified. Using intestinal tumors arising spontaneously and induced by X-rays in CBA/H × C57BL/6J F1 hybrid mice and high-resolution microsatellite loss of heterozygosity (LOH) techniques, we provide mapping data for wt Apc loss, which confirms and extends earlier observations. In addition, high-frequency loss events at the Dpc4 locus were found in both spontaneous and radiation-induced tumors. These data identified LOH of Dpc4 as a critical secondary event following complete functional loss of Apc. LOH across the Trp53 genomic region of chromosome 11 was not observed. No LOH was recorded for the Mom1 candidate gene Pla2g2a or for 9 out of 10 polymorphic markers from the Mom1 genomic region on murine chromosome 4. One marker mapping distal to Pla2g2a showed LOH in a small minority of spontaneous tumors. These data support the contention that Mom1 does not act as a classical tumor suppressor. Overall, our data indicates a significant role for Dpc4 mutation in intestinal tumor progression in the mouse and provides further evidence for the importance of interstitial chromosome losses in radiation tumorigenesis. Genes, Chromosomes and Cancer 28:387–394, 2000. © Crown copyright 2000. Reproduced with the permission of the Controller of Her Majesty's Stationary Office. Citing Literature Volume28, Issue4August 2000Pages 387-394 RelatedInformation