1. MSH2 and Hereditary Nonpolyposis Colorectal Cancer By Bobby Glenn Warren III

2. MutS Homolog 2

3. DNA Mismatch Repair (MMR) Pathways Nuclear Envelope MSH2 MSH6 MSH2MutSα Base mismatch repair and small insertion/deletion loops MSH3 MSH2MutSβ Larger insertion/deletion loops Cytoplasm

4. MMR deficiency (Mutations in the MSH2 gene) gives rise to Microsatellite Instability

5. Nuclear Envelope MSH2 MSH6 MSH2MutSα Base mismatch repair and small insertion/deletion loops MSH3 MSH2MutSβ Larger insertion/deletion loops Cytoplasm Loss of MSH2 function increases mutation frequencies by two to three magnitudes

6. Lynch Syndrome HPNCC is another term for MSH2

7. Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

8. MSH2 and HNPCC

9. Summary MSH2 is required for DNA mismatch repair (MMR) which repairs base pair mismatches and insertion/deletion loops. The loss of MMR, in this case via loss of MSH2, causes an accumulation of mutations. An accumulation of mutations leads to tumorigenesis. Cells dividing more rapidly, such as epithelial cells, will most likely develop cancer first. Since colon epithelial cells divide very rapid, they are the first and most common cancer associated with MMR deficiency.

10. References Ls Gentics HPNCC. (n.d.). Retrieved March 31, 2015, from http://www.lynch-syndrome- uk.org/ls_genetics_.htmlhttp://www.lynch-syndrome- uk.org/ls_genetics_.html MSH2 gene. (n.d.). Retrieved March 31, 2015, from http://ghr.nlm.nih.gov/gene/MSH2 http://ghr.nlm.nih.gov/gene/MSH2 SMH.COM - Understanding Lynch Syndrome. (n.d.). Retrieved March 31, 2015, from http://www.smh.com/p.aspx?p=525 http://www.smh.com/p.aspx?p=525 Tomasetti, C. (2015). Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science, 347(6217), 78-81.