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Working through a diagnostic challenge: colonic polyposis, Amsterdam criteria, and a mismatch repair mutation

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Abstract

The two most common causes of hereditary colorectal cancer are Lynch syndrome and familial adenomatous polyposis (FAP). The phenotype of Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is differentiated in part from FAP by the lack of profuse colonic polyposis. Here we describe a proband who presented with greater than 50 adenomatous colonic polyps prior to developing cancer of the colon and urinary bladder, and a family history that fulfills the Amsterdam criteria. Germline analyses of APC and MYH in the proband did not reveal any mutations. Comprehensive analysis of the mismatch repair genes associated with Lynch syndrome revealed a germline hMSH6 missense mutation 2314C>T (arg772trp) and normal sequencing for hMSH2 and hMLH1. We outline evidence supporting the pathogenicity of the identified hMSH6 mutation (arg772trp) and suggest possible etiologies for the unexplained colonic adenomatous polyposis.

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Abbreviations

FAP:

Familial adenomatous polyposis

HNPCC:

Hereditary nonpolyposis colorectal cancer

AFAP:

Attenuated familial adenomatous polyposis

MAP:

MYH-associated polyposis

MMR:

Mismatch repair

MSI:

Microsatellite instability

MSI-L:

Low level of MSI

IHC:

Immunohistochemistry

CLIA:

Clinical Laboratory Improvement Amendments

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Acknowledgements

The family’s participation in the study is gratefully acknowledged. This research was supported in part by a General Clinical Research Center grant from NIH (M01 RR00043) awarded to the City of Hope National Medical Center, Duarte, California, and by the National Cancer Institute, Grant No. R25 CA85771.

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Authors and Affiliations

  1. Department of Clinical Cancer Genetics, City of Hope National Medical Center, Duarte, CA, USA

    Kory W. Jasperson, Kathleen R. Blazer, Katrina Lowstuter & Jeffrey N. Weitzel

  2. High Risk Cancer Clinics, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Room 3145, Salt Lake City, UT, 84112, USA

    Kory W. Jasperson

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  1. Kory W. Jasperson
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  2. Kathleen R. Blazer
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  3. Katrina Lowstuter
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  4. Jeffrey N. Weitzel
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Correspondence to Kory W. Jasperson.

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Jasperson, K.W., Blazer, K.R., Lowstuter, K. et al. Working through a diagnostic challenge: colonic polyposis, Amsterdam criteria, and a mismatch repair mutation. Familial Cancer 7, 281–285 (2008). https://doi.org/10.1007/s10689-007-9179-z

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  • DOI: https://doi.org/10.1007/s10689-007-9179-z

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