Oncogenic KRAS is not necessary for Wnt signalling activation in APC-associated FAP adenomas
dc.contributor.author | Obrador-Hevia, Antònia | en_US |
dc.contributor.author | Chin, Suet-Feung | en_US |
dc.contributor.author | González, Sara | en_US |
dc.contributor.author | Rees, Jonathan | en_US |
dc.contributor.author | Vilardell, Felip | en_US |
dc.contributor.author | Greenson, Joel K. | en_US |
dc.contributor.author | Cordero, David | en_US |
dc.contributor.author | Moreno, Víctor | en_US |
dc.contributor.author | Caldas, Carlos | en_US |
dc.contributor.author | Capellá, Gabriel | en_US |
dc.date.accessioned | 2010-04-14T20:03:51Z | |
dc.date.available | 2011-03-01T16:26:45Z | en_US |
dc.date.issued | 2010-05 | en_US |
dc.identifier.citation | Obrador-Hevia, AntÒnia; Chin, Suet-Feung; GonzÁlez, Sara; Rees, Jonathan; Vilardell, Felip; Greenson, Joel K; Cordero, David; Moreno, VÍctor; Caldas, Carlos; CapellÁ, Gabriel (2010). "Oncogenic KRAS is not necessary for Wnt signalling activation in APC-associated FAP adenomas No conflicts of interest were declared. ." The Journal of Pathology 221(1): 57-67. <http://hdl.handle.net/2027.42/69187> | en_US |
dc.identifier.issn | 0022-3417 | en_US |
dc.identifier.issn | 1096-9896 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/69187 | |
dc.description.abstract | Recent studies have suggested that APC loss alone may be insufficient to promote aberrant Wnt/Β-catenin signalling. Our aim was to comprehensively characterize Wnt signalling components in a set of APC-associated familial adenomatous polyposis (FAP) tumours. Sixty adenomas from six FAP patients with known pathogenic APC mutations were included. Somatic APC and KRAS mutations, Β-catenin immunostaining, and qRT-PCR of APC, MYC, AXIN2 and SFRP1 were analysed. Array-comparative genomic hybridization (aCGH) was also assessed in 26 FAP adenomas and 24 paired adenoma–carcinoma samples. A somatic APC alteration was present in 15 adenomas (LOH in 11 and four point mutations). KRAS mutations were detected in 10% of the cases. APC mRNA was overexpressed in adenomas. MYC and AXIN2 were also overexpressed, with significant intra-case heterogeneity. Increased cytoplasmic and/or nuclear Β-catenin staining was seen in 94% and 80% of the adenomas. Β-Catenin nuclear staining was strongly associated with MYC levels ( p value 0.03) but not with KRAS mutations. Copy number aberrations were rare. However, the recurrent chromosome changes observed more frequently contained Wnt pathway genes ( p value 0.012). Based on Β-catenin staining and Wnt pathway target genes alterations the Wnt pathway appears to be constitutively activated in all APC-FAP tumours, with alterations occurring both upstream and downstream of APC. Wnt aberrations are present at both the DNA and the RNA level. Somatic profiling of APC-FAP tumours provides new insights into the role of APC in tumourigenesis. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. | en_US |
dc.format.extent | 436608 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | John Wiley & Sons, Ltd. | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Cancer Research, Oncology and Pathology | en_US |
dc.title | Oncogenic KRAS is not necessary for Wnt signalling activation in APC-associated FAP adenomas | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Pathology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan Heath System, Ann Arbor, USA | en_US |
dc.contributor.affiliationother | Cancer Cell Biology Group, Institut Universitari d'InvestigaciÓ en CiÈncies de la Salut (IUNICS)—Universitat de les Illes Balears, Mallorca, Illes Balears, Spain | en_US |
dc.contributor.affiliationother | CRUK Cambridge Research Institute. Li Ka Shing Centre. Robinson Way, Cambridge CB2 0RE, UK | en_US |
dc.contributor.affiliationother | Laboratori de Recerca Translacional, Departament de PrevenciÓ i Control del CÀncer, Servei d'Epidemiologia i Registre del CÀncer, IDIBELL—Institut CatalÀ d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain | en_US |
dc.contributor.affiliationother | Department of Colorectal Surgery, Gloucestershire Royal Hospital, Gloucestershire Hospitals NHS Foundation Trust, Great Western Road, Gloucester, UK | en_US |
dc.contributor.affiliationother | Laboratori de Recerca Translacional, Departament de PrevenciÓ i Control del CÀncer, Servei d'Epidemiologia i Registre del CÀncer, IDIBELL—Institut CatalÀ d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain | en_US |
dc.contributor.affiliationother | Laboratori de Recerca Translacional, Departament de PrevenciÓ i Control del CÀncer, Servei d'Epidemiologia i Registre del CÀncer, IDIBELL—Institut CatalÀ d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain | en_US |
dc.contributor.affiliationother | Laboratori de Recerca Translacional, Departament de PrevenciÓ i Control del CÀncer, Servei d'Epidemiologia i Registre del CÀncer, IDIBELL—Institut CatalÀ d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain | en_US |
dc.contributor.affiliationother | CRUK Cambridge Research Institute. Li Ka Shing Centre. Robinson Way, Cambridge CB2 0RE, UK | en_US |
dc.contributor.affiliationother | Laboratori de Recerca Translacional, Departament de PrevenciÓ i Control del CÀncer, Servei d'Epidemiologia i Registre del CÀncer, IDIBELL—Institut CatalÀ d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain ; Laboratori de Recerca Translacional, Institut CatalÀ d'Oncologia, Barcelona, Spain | en_US |
dc.identifier.pmid | 20196079 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/69187/1/2685_ftp.pdf | |
dc.identifier.doi | 10.1002/path.2685 | en_US |
dc.identifier.source | The Journal of Pathology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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