1 / 13

MSH2 and Hereditary Nonpolyposis Colon Cancer

MSH2 and Hereditary Nonpolyposis Colon Cancer. Keri Nakao 5 April 2005. Hereditary Nonpolyposis Colorectal Cancer. Tumors on proximal (right side) colon Tumors in gastrointestinal tract and genitourinary tract often Muir-Torre. http://ghr.nlm.nih.gov/gene=msh2. MSH2 located on Chromosome 2.

diane
Download Presentation

MSH2 and Hereditary Nonpolyposis Colon Cancer

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. MSH2 and Hereditary Nonpolyposis Colon Cancer Keri Nakao 5 April 2005

  2. Hereditary Nonpolyposis Colorectal Cancer • Tumors on proximal (right side) colon • Tumors in gastrointestinal tract and genitourinary tract often • Muir-Torre http://ghr.nlm.nih.gov/gene=msh2

  3. MSH2 located on Chromosome 2 Location – 2p22-p21 Cell. 1993 Dec 3;75(5):1027-38. Fishel et al. k-12.pisd.edu/.../ Genetic/Chromosome-02.htm

  4. Mismatch Repair System • MSH2 and MSH6 bind to mismatched segment of DNA • DNA helicase unwinds helix • MLH1 endonuclease binds to complex and excises replication error • DNA polymerase fills gap • DNA ligase Lodish et al. Fig. 23-28

  5. Insertion-Deletion Loops www.sci.sdsu.edu/.../ mutations/deletions.html

  6. MSH2 Gene Mapping genome.chmcc.org/.../ SNProtein/Polydom.html

  7. MSH2 Structure Cell. 1997 Dec 26;91(7):995-1005. Gradia et al.

  8. Knockout Mice MSH2 -/- Nature Genetics. 1995 Sep;11(1):64-70. Reitmair et al. Cell. 1995 Jul 28;82(2):321-30. de Wind et al.

  9. Knockouts tolerant to MNNG • MNNG induces: • chromosomal aberrations • Sister chromosome exchanges • DNA strand breaks • Unscheduled DNA synthesis www.uoguelph.ca/.../ 4426/Mutagenesis6.html http://monographs.iarc.fr/htdocs/monographs/suppl7/mnng.html

  10. HNPCC www.healingdaily.com/.../ colon-health.htm

  11. Mutations in MSH2 • Deletions in poly(dA/dT) sequences and other simple repeats • Frameshifts or point mutations that result in STOP codons • Missense American Journal of Human Genetics. 1995 May;56(5):1060-6. Wijnen et al. Human Genetics. 1996 Feb;97(2):251-5. Maliaka et al.

  12. Treatment • Family testing • Risk is significantly higher in males • Aspirin or Suldinac Proceedings of the National Academy of Science of the U S A. 1998 Sep 15;95(19):11301-6. Ruschoff et al.

  13. Summary • Mismatch Repair System • Knockout mice viable but develop lymphomas • Many mutations in MSH2 may cause HNPCC

More Related