Genomes and Genes
Affiliation: Loyola University Medical Center
- The APC gene in colorectal cancerR Fodde
Department of Human and Clinical Genetics, LUMC, Sylvius Laboratories, Leiden, The Netherlands
Eur J Cancer 38:867-71. 2002....
- E-cadherin and adenomatous polyposis coli mutations are synergistic in intestinal tumor initiation in miceR Smits
Medical Genetics Center, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
Gastroenterology 119:1045-53. 2000..In addition, loss or haploinsufficiency of E-cadherin may affect tumorigenesis by altering its cell-adhesive and associated functions...
- Mutations in the APC tumour suppressor gene cause chromosomal instabilityR Fodde
Department of Human and Clinical Genetics, and Center for Biomedical Genetics, Leiden University Medical Center, PO Box 9503, 2300 RA Leiden, The Netherlands
Nat Cell Biol 3:433-8. 2001..We conclude that loss of APC sequences that lie C-terminal to the beta-catenin regulatory domain contributes to chromosomal instability in colorectal cancer...
- Disease model: familial adenomatous polyposisR Fodde
Dept of Human and Clinical Genetics, Leiden University Medical Center, Sylvius Laboratories, Wassenaarseweg 72, 2333 AL, Leiden, The Netherlands
Trends Mol Med 7:369-73. 2001..Also, the close phenotypic resemblance to the human disease makes these mice unique preclinical models to test chemopreventive and therapeutic interventions...
- Dynamic expression and nuclear accumulation of beta-catenin during the development of hair follicle-derived structuresM Ridanpaa
Department of Human and Clinical Genetics, Leiden University Medical Center LUMC, 72, 2333 AL, Wassenaarseweg, The Netherlands
Mech Dev 109:173-81. 2001..These results further elucidate the role of the Wnt signal transduction pathway during hair follicle related development and tumorigenesis and illustrate the dynamic role of beta-catenin in signal transduction and cell-adhesion...
- APC, signal transduction and genetic instability in colorectal cancerR Fodde
Department of Human and Clinical Genetics, and Center for Biomedical Genetics, Leiden University Medical Center, The Netherlands
Nat Rev Cancer 1:55-67. 2001..Inactivation of APC--the gene responsible for most cases of colorectal cancer--might fulfil both requirements...
- Somatic Apc mutations are selected upon their capacity to inactivate the beta-catenin downregulating activityR Smits
MGC Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
Genes Chromosomes Cancer 29:229-39. 2000..These results indicate that somatic Apc mutations are selected during intestinal tumorigenesis and that inactivation of the beta-catenin downregulating function of APC is likely to represent the main selective factor...
- A targeted mouse Brca1 mutation removing the last BRCT repeat results in apoptosis and embryonic lethality at the headfold stageP Hohenstein
Department of Human and Clinical Genetics, Leiden University Medical Center, P O Box 9503, 2300 RA, The Netherlands
Oncogene 20:2544-50. 2001..5 dpc due to massive apoptosis throughout the embryo. These results indicate that a C-terminal truncating Brca1 mutation removing the last BRCT repeat has a different effect on normal cell function than does the complete absence of Brca1...
- Mechanisms of APC-driven tumorigenesis: lessons from mouse modelsR Fodde
MGC Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
Cytogenet Cell Genet 86:105-11. 1999..Here we review the major features of the available animal models for FAP and attempt the formulation of a hypothetical model for APC-driven tumorigenesis based on the observed genetic and phenotypic variability in mouse and man...
- Molecular analysis of the APC gene in 105 Dutch kindreds with familial adenomatous polyposis: 67 germline mutations identified by DGGE, PTT, and southern analysisR B Van der Luijt
MGC Department of Human Genetics, Sylvius Laboratories, Medical Faculty, Leiden University, The Netherlands
Hum Mutat 9:7-16. 1997..We found that the combined use of the currently available molecular approaches still fails to identify the underlying genetic defect in a significant subset of the FAP families. The possible causes for this limitation are discussed...
- Rapidly progressive adenomatous polyposis in a patient with germline mutations in both the APC and MLH1 genes: the worst of two worldsR Scheenstra
Department of Paediatric Gastroenterology, University Hospital Groningen, The Netherlands
Gut 52:898-9. 2003..Subsequent loss of function of the MLH1 gene, as shown by absent immunostaining of its protein in adenomas with high grade dysplasia, may well have caused the rapid progression to high grade dysplasia in many of the adenomas...
- Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP)M Nielsen
J Med Genet 42:e54. 2005..The frequent occurrence of additional extraintestinal manifestations, such as breast cancer among female MAP patients, should be thoroughly investigated...
- Smad4 haploinsufficiency in mouse models for intestinal cancerP Alberici
Department of Pathology, Josephine Nefkens Institute, ErasmusMC, Rotterdam, The Netherlands
Oncogene 25:1841-51. 2006..Moreover, complete loss of Smad4 strongly enhances Apc-driven tumor formation...
- Expression and genomic profiling of colorectal cancerJ Cardoso
Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Center, 3000CA Rotterdam, The Netherlands
Biochim Biophys Acta 1775:103-37. 2007....
- Hereditary desmoid disease due to a frameshift mutation at codon 1924 of the APC geneD M Eccles
Wessex Clinical Genetics Service, Southampton University Hospital Trust
Am J Hum Genet 59:1193-201. 1996..We show that HDD segregates with an unusual germ-line chain-terminating mutation at the 3' end of the APC gene (codon 1924) with somatic loss of the wild-type allele leading to tumor development...
- Loss of Apc and the entire chromosome 18 but absence of mutations at the Ras and Tp53 genes in intestinal tumors from Apc1638N, a mouse model for Apc-driven carcinogenesisR Smits
MGC Department of Human Genetics, Leiden University, The Netherlands
Carcinogenesis 18:321-7. 1997....
- A mouse model of human familial adenomatous polyposisK Yang
Strang Cancer Prevention Center, New York Hospital Cornell Medical Center, New York 10021, USA
J Exp Zool 277:245-54. 1997..These results suggest that mice carrying the Apc1638 mutation can serve as a good model to study the initiation, progression, and inhibition of gastrointestinal tumors...
- Short-term carcinogenicity testing of a potent murine intestinal mutagen, 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), in Apc1638N transgenic miceI K Sørensen
National Food Agency, Institute of Toxicology, Søborg, Denmark
Carcinogenesis 18:777-81. 1997..No differences in intestinal and mammary tumor multiplicity were observed between treated and control Apc+/Apc1638N females...
- Apc1638N: a mouse model for familial adenomatous polyposis-associated desmoid tumors and cutaneous cystsR Smits
Medical Genetics Center South West Netherlands, Department of Human Genetics, Leiden University
Gastroenterology 114:275-83. 1998..Although by definition desmoids are nonmalignant, because of their aggressive invasion of local structures, they represent one of the major causes of morbidity and mortality among patients with FAP...
- Clinical findings with implications for genetic testing in families with clustering of colorectal cancerJ T Wijnen
Department of Human Genetics, Leiden University Medical Center, The Netherlands
N Engl J Med 339:511-8. 1998..We assessed the prevalence of MSH2 and MLH1 mutations in families suspected of having hereditary nonpolyposis colorectal cancer and evaluated whether clinical findings can predict the outcome of genetic testing...
- A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancerC R Boland
University of California, San Diego, La Jolla 92093 0688, USA
Cancer Res 58:5248-57. 1998..f) The spectrum of microsatellite alterations in noncolonic tumors was reviewed, and it was concluded that the above recommendations apply only to colorectal neoplasms. (g) A research agenda was recommended...
- Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathwayV J Wielenga
Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands
Am J Pathol 154:515-23. 1999..Our results indicate that CD44 expression is part of a genetic program controlled by the beta-catenin/Tcf-4 signaling pathway and suggest a role for CD44 in the generation and turnover of epithelial cells...
- Intestinal tumorigenesis in the Apc1638N mouse treated with aspirin and resistant starch for up to 5 monthsS L Williamson
Department of Histopathology, Royal Victoria Infirmary, Newcastle upon Tyne, UK
Carcinogenesis 20:805-10. 1999..However, it remains possible that any increased risk is restricted to carriers of germline mutations in APC...
- A germline mutation at the extreme 3' end of the APC gene results in a severe desmoid phenotype and is associated with overexpression of beta-catenin in the desmoid tumorJ Couture
Department of Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada
Clin Genet 57:205-12. 2000..The natural history of the disease is variable between individuals, and surgical interventions have to be timed appropriately due to the frequent recurrences...
- Tumour-stroma interactions in colorectal cancer: converging on beta-catenin activation and cancer stemnessN H Le
Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Centre, Erasmus MC, Rotterdam, The Netherlands
Br J Cancer 98:1886-93. 2008..As such, the tumour microenvironment is likely to maintain the cancer stem cell phenotype in a subset of cells, thus mediating invasion and metastasis...