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Research Article

Specific Variants in the MLH1 Gene Region May Drive DNA Methylation, Loss of Protein Expression, and MSI-H Colorectal Cancer

  • Miralem Mrkonjic,

    Affiliations: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

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  • Nicole M. Roslin,

    Affiliation: Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada

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  • Celia M. Greenwood,

    Affiliations: Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

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  • Stavroula Raptis,

    Affiliations: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

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  • Aaron Pollett,

    Affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

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  • Peter W. Laird,

    Affiliation: University of Southern California Epigenome Center, University of Southern California, Los Angeles, California, United States of America

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  • Vaijayanti V. Pethe,

    Affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

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  • Theodore Chiang,

    Affiliation: Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada

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  • Darshana Daftary,

    Affiliation: Ontario Familial Colorectal Cancer Registry, Cancer Care Ontario, Toronto, Ontario, Canada

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  • Elizabeth Dicks,

    Affiliation: Clinical Epidemiology Unit, Memorial University of Newfoundland, St. John's, Newfoundland, Canada

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  • Stephen N. Thibodeau,

    Affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America

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  • Steven Gallinger,

    Affiliations: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, Ontario Familial Colorectal Cancer Registry, Cancer Care Ontario, Toronto, Ontario, Canada, Department of Surgery, University of Toronto, Toronto, Ontario, Canada

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  • Patrick S. Parfrey,

    Affiliation: Clinical Epidemiology Unit, Memorial University of Newfoundland, St. John's, Newfoundland, Canada

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  • H. Banfield Younghusband,

    Affiliation: Discipline of Genetics, Memorial University of Newfoundland, St. John's, Newfoundland, Canada

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  • John D. Potter,

    Affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington, United States of America

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  • Thomas J. Hudson,

    Affiliations: Ontario Institute for Cancer Research, Toronto, Ontario, Canada, Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

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  • John R. McLaughlin,

    Affiliations: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada, Ontario Familial Colorectal Cancer Registry, Cancer Care Ontario, Toronto, Ontario, Canada

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  • Roger C. Green,

    Affiliation: Discipline of Genetics, Memorial University of Newfoundland, St. John's, Newfoundland, Canada

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  • Brent W. Zanke,

    Affiliations: Ontario Familial Colorectal Cancer Registry, Cancer Care Ontario, Toronto, Ontario, Canada, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

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  • Polly A. Newcomb,

    Affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington, United States of America

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  • Andrew D. Paterson,

    Affiliations: Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

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  • Bharati Bapat mail

    bapat@lunenfeld.ca

    Affiliations: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

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  • Published: October 13, 2010
  • DOI: 10.1371/journal.pone.0013314

About the Authors

Miralem Mrkonjic, Stavroula Raptis, Steven Gallinger, Bharati Bapat
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Miralem Mrkonjic, Stavroula Raptis, Vaijayanti V. Pethe, Steven Gallinger, John R. McLaughlin, Bharati Bapat
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
Miralem Mrkonjic, Stavroula Raptis, Aaron Pollett, Bharati Bapat
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
Nicole M. Roslin, Celia M. Greenwood, Theodore Chiang, Andrew D. Paterson
Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada
Celia M. Greenwood, John R. McLaughlin, Andrew D. Paterson
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
Peter W. Laird
University of Southern California Epigenome Center, University of Southern California, Los Angeles, California, United States of America
Darshana Daftary, Steven Gallinger, John R. McLaughlin, Brent W. Zanke
Ontario Familial Colorectal Cancer Registry, Cancer Care Ontario, Toronto, Ontario, Canada
Elizabeth Dicks, Patrick S. Parfrey
Clinical Epidemiology Unit, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
Stephen N. Thibodeau
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America
Steven Gallinger
Department of Surgery, University of Toronto, Toronto, Ontario, Canada
H. Banfield Younghusband, Roger C. Green
Discipline of Genetics, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
John D. Potter, Polly A. Newcomb
Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington, United States of America
Thomas J. Hudson
Ontario Institute for Cancer Research, Toronto, Ontario, Canada
Thomas J. Hudson
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
Thomas J. Hudson
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
Brent W. Zanke
Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

Corresponding Author

Email: bapat@lunenfeld.ca

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: MM NMR CMTG AP BB. Performed the experiments: MM SR AFP PWL VP. Analyzed the data: MM NMR CMTG TC. Contributed reagents/materials/analysis tools: CMTG DD ED ST SG PSP HBY JP TJH JRM RCG BZ PAN AP BB. Wrote the paper: MM NMR JP PAN AP BB.