Chromosomal instability & MUTYH pathways

Topic Completed: 1 September 2010

Minor changes: 17 April 2021

Copyright: 2003-2021,, Inc.

PubMed Search: Chromosome AND "instability pathway"

Shilpa Jain, M.D.
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Cite this page: Jain S. Chromosomal instability & MUTYH pathways. website. Accessed October 28th, 2021.
Chromosomal instability pathway
  • Common pathway in colorectal carcinoma
  • Mutations in oncogenes and tumor suppressor genes, including APC, beta catenin, Kras, BRAF, SMAD4, PTEN, p53 and bax
  • Have altered total DNA content, cytogenetics, aneuploidy and numerous allelic gains and losses and translocations
  • 70% + of colorectal carcinomas (Neoplasia 2008;10:680)
  • Etiology
  • Clinical features:
    • Important in familial adenomatous polyposis and variants (APC gene) and juvenile polyposis (DPC4, PTEN genes)
    • High rate of concordance for Kras status between primaries and metastases (Oncologist. 2008;13:1270)
    • Patterns of Kras mutation vary based on germline mismatch repair defects and hMLH1 methylation status (Hum Mol Genet 2004;13:2303)
    • Updated National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Colon Cancer now recommend that tumors from all patients with stage IV disease be tested for the Kras gene
    • Only patients whose tumors have normal (wild type) Kras should receive cetuximab and panitumumab
MUTYH pathway
  • See also MUTYH associated polyposis
  • MUTYH (also called MYH) gene encodes MUTYH glycosylase, involved in oxidative DNA damage repair (Wikipedia)
  • Mutations occur in both copies of MUTYH repair gene
  • Genetic pathway is not well understood (Curr Genomics 2008;9:420)
  • Biallelic patients (mutations in both genes) have multiple adenomas (Hum Mutat 2006;27:1064) and 93× excess risk of colorectal carcinoma compared to normal controls but account for < 1% of all cases (Am J Hum Genet 2005;77:112)
  • Germline mutation of MUTYH gene is a mechanism of development of APC negative familial adenomatous polyposis; these patients may have a family history compatible with recessive inheritance indicating that this may be a different disease; genetic testing may be helpful in screening, diagnosis and management of atypical FAP cases
  • Can be detected by high resolution melting analysis
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