Germline MYH mutations in a clinic-based series of Canadian multiple colorectal adenoma patientsMarina E Croitoru
Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
J Surg Oncol 95:499-506. 2007
..Our objective was to determine the significance of MYH mutations in a series of Canadian patients with multiple adenomas...
- Suppression of nuclear Wnt signaling leads to stabilization of Rac1 isoforms
Susmita Esufali
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray Street, Room L6 304 4, Toronto, Canada
FEBS Lett 581:4850-6. 2007
..In addition, we show that Rac1b may be under proteasomal regulation. We propose that Rac1 and Rac1b levels are regulated by being targeted for degradation through a negative feedback loop initiated by Wnt signaling...
Cyclin D1 Pro241Pro (CCND1-G870A) polymorphism is associated with increased cancer risk in human populations: a meta-analysisNoel Pabalan
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 60 Murray Street, Room L6 304, Box 29, Toronto, Ontario, Canada M5T 3L9
Cancer Epidemiol Biomarkers Prev 17:2773-81. 2008
..6-7.1). In conclusion, our study strongly supports the increased cancer risk associated with CCND1-A870G polymorphism in the human population...
- A large novel deletion in the APC promoter region causes gene silencing and leads to classical familial adenomatous polyposis in a Manitoba Mennonite kindred
George S Charames
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray St, Toronto, Box 30, ON, M5T 3L9, Canada
Hum Genet 124:535-41. 2008
..This study strengthens the likelihood that this novel APC promoter mutation is linked to this unique population as a founder mutation...
- Rac1b recruits Dishevelled and β-catenin to Wnt target gene promoters independent of Wnt3A stimulation
Vaijayanti V Pethe
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5T 3L9, Canada
Int J Oncol 39:805-10. 2011
..Our studies suggest a novel transcriptional co-activator role of Rac1b in β-catenin/TCF-mediated transcription...
The association of tumor microsatellite instability phenotype with family history of colorectal cancerBharati Bapat
Department of Pathology and Lab Medicine, Mount Sinai Hospital, and Samuel Lunenfeld Research Institute, University of Toronto, 60 Murray Street, Box 30, Toronto, M5T 3L9, Ontario, Canada
Cancer Epidemiol Biomarkers Prev 18:967-75. 2009
..Familial risk associated with MSI-High tumors is primarily driven by the Amsterdam-criteria patients. MSI-Low tumors may represent a distinct subtype of colorectal cancer with respect to certain epidemiologic variables studied here...
- Association of tissue promoter methylation levels of APC, TGFβ2, HOXD3 and RASSF1A with prostate cancer progression
Liyang Liu
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
Int J Cancer 129:2454-62. 2011
..017). Our study demonstrated that quantitative increase in promoter methylation levels of APC, HOXD3 and TGFβ2 are associated with PCa progression...
- Vitamin D intake is negatively associated with promoter methylation of the Wnt antagonist gene DKK1 in a large group of colorectal cancer patients
James B Rawson
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
Nutr Cancer 64:919-28. 2012
..001) and a similar trend was observed in Ontario. These results suggest that vitamin D and other dietary/lifestyle factors may alter CRC risk by mediating extracellular Wnt inhibition...
- MSH2 118T>C and MSH6 159C>T promoter polymorphisms and the risk of colorectal cancer
Miralem Mrkonjic
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario M5T 3L9, Canada
Carcinogenesis 28:2575-80. 2007
..003 and P = 0.0001, respectively). The MSH2 -118T>C polymorphism was associated with strong family history of CRC in Ontario patients...
- Promoter methylation of Wnt antagonists DKK1 and SFRP1 is associated with opposing tumor subtypes in two large populations of colorectal cancer patients
James B Rawson
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Carcinogenesis 32:741-7. 2011
..This is the first large study to identify associations between Wnt antagonist promoter hypermethylation and CRC MSI subtype. These events provide insight into subtype-specific epigenetic mediation of Wnt signaling in CRC...
- Prognostic value of molecular markers, sub-stage and European Organisation for the Research and Treatment of Cancer risk scores in primary T1 bladder cancer
Bas W G van Rhijn
Division of Urology, University Health Network, Princess Margaret Hospital, Toronto, ON, Canada
BJU Int 110:1169-76. 2012
..Future studies may lead to the incorporation of sub-stage (T1m/T1e) in the TNM classification system for urinary BC to guide clinical decision-making in T1 BC...
- Specific variants in the MLH1 gene region may drive DNA methylation, loss of protein expression, and MSI-H colorectal cancer
Miralem Mrkonjic
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
PLoS ONE 5:e13314. 2010
..We hypothesized that specific polymorphisms in the MLH1 gene region predispose it to DNA methylation, resulting in the loss of MLH1 gene expression, mismatch-repair function, and consequently to genome-wide microsatellite instability...
- Functional effects of the MLH1-93G>A polymorphism on MLH1/EPM2AIP1 promoter activity
Sheron Perera
Department of Laboratory Medicine and Pathobiology, University of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 1 King s College Circle, Toronto, ON, Canada
Oncol Rep 25:809-15. 2011
..004) cells. The EMSA results suggest that this polymorphism alters the affinity of nuclear factors that bind to this region. Our findings indicate that the -93G>A polymorphism modifies the efficiency of MLH1/EPM2AIP1 transcription...
- A novel complex mutation in MSH2 contributes to both Muir-Torre and Lynch Syndrome
Sheron Perera
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
J Hum Genet 55:37-41. 2010
....
- Comparison of clinical schemas and morphologic features in predicting Lynch syndrome in mutation-positive patients with endometrial cancer encountered in the context of familial gastrointestinal cancer registries
Paul Ryan
Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada
Cancer 118:681-8. 2012
..In this study, the authors determined the efficacy of family/personal history and tumor morphology in predicting LS in a cohort of patients with EC who had mutation-proven LS...
- Rac1 GTPase and the Rac1 exchange factor Tiam1 associate with Wnt-responsive promoters to enhance beta-catenin/TCF-dependent transcription in colorectal cancer cells
Pinella Buongiorno
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5T 3L9, Canada
Mol Cancer 7:73. 2008
..We hypothesised that Rac1 plays a direct role in enhancing the transcription of endogenous Wnt target genes by modulating the beta-catenin/TCF transcription factor complex...
- Epigenetic biomarkers in colorectal cancer diagnostics
James B Rawson
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, L6 304B, Box 30, Toronto, ON M5G 1X5, Canada
Expert Rev Mol Diagn 12:499-509. 2012
..This review will aim to summarize the established and emerging roles of epigenetic modifications in CRC detection, prognostication and prediction of treatment response...
- A novel and rapid method of determining the effect of unclassified MLH1 genetic variants on differential allelic expression
Sheron Perera
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
J Mol Diagn 12:757-64. 2010
....
- Patients with Lynch syndrome mismatch repair gene mutations are at higher risk for not only upper tract urothelial cancer but also bladder cancer
Sean C Skeldon
Department of Surgical Oncology, Urology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada
Eur Urol 63:379-85. 2013
..An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse...
- Correlation of ERG expression and DNA methylation biomarkers with adverse clinicopathologic features of prostate cancer
Ken Kron
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
Clin Cancer Res 18:2896-904. 2012
..The aim of this study was to analyze the relationship between ERG expression, DNA methylation of three biomarkers, and clinicopathologic features of prostate cancer...
- The MLH1 variants p.Arg265Cys and p.Lys618Ala affect protein stability while p.Leu749Gln affects heterodimer formation
Sheron Perera
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
Hum Mutat 29:332. 2008
..Arg265Cys (c.793C>T) and p.Lys618Ala (c.1852_1853AA>GC) significantly decrease the stability of the protein, while another missense variant p.Leu749Gln (c.2246T>A) is able to compromise heterodimerization of the MLH1-PMS2 complex...
- Quantitative DNA methylation analysis of genes coding for kallikrein-related peptidases 6 and 10 as biomarkers for prostate cancer
Ekaterina Olkhov-Mitsel
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
Epigenetics 7:1037-45. 2012
..A similar trend for KLK6 DNA methylation was observed. The results suggest that KLK6 and KLK10 DNA methylation distinguishes organ confined from locally invasive PCa and may have prognostic value...
- Does early colectomy increase desmoid risk in familial adenomatous polyposis?
Carol Durno
Familial Gastrointestinal Cancer Registry and Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
Clin Gastroenterol Hepatol 5:1190-4. 2007
..We hypothesized that prophylactic colectomy at an early age might increase the risk of developing desmoids. The aim of this study was to determine whether colectomy earlier in life is a risk factor for the development of desmoid tumors...
- MLH1 -93G>A promoter polymorphism and the risk of microsatellite-unstable colorectal cancer
Stavroula Raptis
Department of Pathology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5T 3L9
J Natl Cancer Inst 99:463-74. 2007
..We investigated whether polymorphisms in DNA mismatch repair genes are associated with the risk of colorectal cancer...
- MLH1 region polymorphisms show a significant association with CpG island shore methylation in a large cohort of healthy individuals
Andrea J Savio
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
PLoS ONE 7:e51531. 2012
..These results indicate that CpG island shore methylation in PBCs may be influenced by genotype as well as the normal aging process...
- Epigenetic regulation of kallikrein-related peptidases: there is a whole new world out there
Maria D Pasic
Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada
Biol Chem 393:319-30. 2012
..Experimental validation remains an essential step to confirm the KLK-miRNA interaction. Epigenetic regulation of KLKs holds promise for an array of therapeutic applications in many diseases including cancer...
- The FGFR3 mutation is related to favorable pT1 bladder cancer
Bas W G van Rhijn
Division of Urology, Princess Margaret Hospital, Toronto, Ontario, Canada
J Urol 187:310-4. 2012
..We determined the frequency of FGFR3 mutations and P53 alterations in patients with pT1 bladder cancer and correlated these data to histopathological variables and clinical outcomes...
- DNA methylation of HOXD3 as a marker of prostate cancer progression
Ken J Kron
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
Lab Invest 90:1060-7. 2010
..028). The results indicate that HOXD3 methylation distinguishes low-grade prostate cancers from intermediate and high-grade ones and may also have prognostic value when considered together with pathological stage...
- Strategies for discovery and validation of methylated and hydroxymethylated DNA biomarkers
Ekaterina Olkhov-Mitsel
Samuel Lunenfeld Research Institute, Mount Sinai Hospital Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto, Ontario, Canada
Cancer Med 1:237-60. 2012
..The development of DNA methylation- and hydroxymethylation-based biomarkers is an exciting and rapidly evolving area of research that holds promise for potential applications in diverse clinical settings...
- Activation of tumor-specific splice variant Rac1b by dishevelled promotes canonical Wnt signaling and decreased adhesion of colorectal cancer cells
Susmita Esufali
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
Cancer Res 67:2469-79. 2007
....
- Methylation of adenomatous polyposis coli in endometrial cancer occurs more frequently in tumors with microsatellite instability phenotype
Michele Zysman
Samuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
Cancer Res 62:3663-6. 2002
..Our results demonstrate APC methylation in endometrial cancer for the first time and show that APC hypermethylation occurs at an increased frequency in MSI+ endometrial tumors (P = 0.01)...
- Hereditary nonpolyposis colorectal cancer--molecular basis
Christine Brezden-Masley
Department of Surgery, Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
Surgery 134:29-33. 2003
- An association between the 4G polymorphism in the PAI-1 promoter and the development of aggressive fibromatosis (desmoid tumor) in familial adenomatous polyposis patients
Catherine F Li
Program in Developmental Biology, The Hospital for Sick Children, University of Toronto, Ontario, Canada
Fam Cancer 6:89-95. 2007
..This data provides additional evidence supporting an important role for PAI-1 in the pathogenesis of aggressive fibromatosis...
- Cyclooxygenase-2 knockdown by RNA interference in colon cancer
George S Charames
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
Int J Oncol 28:543-9. 2006
....
- MYH mutations are rare in prostate cancer
Eyun Jung Shin
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
J Cancer Res Clin Oncol 133:373-8. 2007
..A compromised base-excision repair function due to defective MYH may contribute to prostate carcinogenesis. Here, we examine the genetic contribution of MYH to prostate cancer risk...
- Discovery of novel hypermethylated genes in prostate cancer using genomic CpG island microarrays
Ken Kron
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
PLoS ONE 4:e4830. 2009
..Such occurrences often lead to the silencing of these key genes and thus they may contribute to the development of cancer, including prostate cancer...
- Considerations when analyzing the methylation status of PTEN tumor suppressor gene
Michele A Zysman
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
Am J Pathol 160:795-800. 2002
..Without careful consideration of the critical nucleotide differences between the two sequences, results obtained from PTEN analysis may not necessarily represent the methylation status of PTEN...
