Hereditary Nonpolyposis Colorectal Cancer

Ian Frayling, Addenbrooke's Hospital, Cambridge, UK

Published online: January 2006

DOI: 10.1038/npg.els.0005965

An inherited cancer predisposition syndrome characterized clinically by a propensity to colorectal, endometrial and other tumors, and molecularly by germline mutations in DNA mismatch repair genes.

Keywords: colon; rectum; endometrium; Lynch syndrome; microsatellite instability; mismatch repair

Figure 1. Immunohistochemistry of DNA mismatch repair proteins in a colorectal cancer from an HNPCC patient with a germ-line mutation in MLH1. The top panels (a,c) show low-power views, the lower panels (b,d) show high-power views. Antibodies specific to either MSH2 (a,b) or MLH1 (c,d), which have bound to the tissues, are stained red-brown; nonspecific blue counterstaining is used to show tissue not expressing MSH2 or MLH1. Note that normal tissue (gc) expresses both proteins, as do normal lymphocytes in the stroma surrounding the cancer (n). However, while the cancer cells (Ca) stain strongly for MSH2 (a,b), they lack MLH1 (c,d). Ca: cancer cells; gc: lymphoid germinal centers; n: normal lymphocytes. (Photographs courtesy of Dr Mark Arends, University of Cambridge.)
Figure 2. DNA mismatch repair in humans. A complex of MSH2–MSH6 binds to point mismatches (a), whereas a complex of MSH2–MSH3 binds to insertion–deletion loops (b). These complexes, bound to mismatched DNA, then bind complexes of MLH1 with either PMS2 or PMS1. The mismatches are then resolved, and repair is achieved.
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 References
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    Jass JR (1998) Diagnosis of hereditary non-polyposis colorectal cancer. Histopathology 32: 491–497. Review.
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    Muller A and Fishel R (2002) Mismatch repair and the hereditary non-polyposis colorectal cancer syndrome (HNPCC). Cancer Investigation 20: 102–109 (review).
    Peltomaki P (2001) DNA mismatch repair and cancer. Mutation Research 488: 77–85 (review).
    Tomlinson I and Bodmer W (1999) Selection, the mutation rate and cancer: ensuring that the tail does not wag the dog. Nature Medicine 5: 11–12. (review).
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 Web Links
    ePath MutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); Locus ID: 4292. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4292
    ePath MutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); Locus ID: 4436. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4436
    ePath MutS homolog 6 (E. coli) (MSH6); Locus ID: 2956. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2956
    ePath PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2); Locus ID: 5395. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5395
    ePath MutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); MIM number: 120436. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?120436
    ePath MutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); MIM number: 120435. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?120435
    ePath MutS homolog 6 (E. coli) (MSH6); MIM number: 600678. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600678
    ePath PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2); MIM number: 600259. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600259

Related Sub-Topics:

Cell Biology of Cancer | Molecular Genetics of Common and Complex Disease | Specific Genetic Disorders | Mutational Mechanisms of Genetic Disease | Cancer Genetics | DNA Damage and Repair
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Article Title: Hereditary Nonpolyposis Colorectal Cancer
 
How to Cite close
Frayling, Ian(Jan 2006) Hereditary Nonpolyposis Colorectal Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005965]