UNIT 10.12 Genetic Testing for Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

  1. Madhuri R. Hegde1,
  2. Benjamin B. Roa2

Published Online: 1 APR 2009

DOI: 10.1002/0471142905.hg1012s61

Current Protocols in Human Genetics

Current Protocols in Human Genetics

How to Cite

Hegde, M. R. and Roa, B. B. 2009. Genetic Testing for Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Current Protocols in Human Genetics. 61:10.12:10.12.1–10.12.28.

Author Information

  1. 1

    Emory University, Atlanta, Georgia

  2. 2

    Myriad Genetic Laboratories, Salt Lake City, Utah

Publication History

  1. Published Online: 1 APR 2009
  2. Published Print: APR 2009


Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome that confers an elevated risk of early-onset colorectal cancer (CRC) and increased lifetime risk for other cancers of the endometrium, stomach, small intestine, hepatobiliary system, kidney, ureter, and ovary. HNPCC accounts for up to 5% of all CRC, making it the most common hereditary colorectal cancer syndrome. Germline mutations in methyl-directed mismatch repair (MMR) genes give rise to microsatellite instability (MSI) in tumor DNA. HNPCC is most often associated with mutations in the MLH1 gene on 3p21, the MSH2 gene on 2p21, and to a lesser extent MSH6 on 2p16. This unit presents a comprehensive molecular and genetic screening strategy for HNPCC mutations in the MLH1, MSH2, and MSH6 genes, including analysis of MSI, mutation scanning by denaturing high-pressure liquid chromatography (DHPLC), and DNA sequencing analysis. Curr. Protoc. Hum. Genet. 61:10.12.1-10.12.28. © 2009 by John Wiley & Sons, Inc.


  • MSI;
  • IHC;
  • MMR genes;
  • MLH1;
  • MSH2;
  • MSH6;
  • microsatellite instability;
  • mutation detection;
  • mutation scanning;
  • DHPLC;
  • sequencing