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Transcript
MSH2 and Hereditary
Nonpolyposis Colorectal Cancer
By Bobby Glenn Warren III
MutS Homolog 2
DNA Mismatch Repair (MMR) Pathways
MSH2
MSH6 MSH2
MutSα
Cytoplasm
Nuclear Envelope
MSH3 MSH2
Larger
insertion/deletion
loops
MutSβ
Base mismatch repair
and small
insertion/deletion
loops
MMR deficiency (Mutations in the MSH2 gene) gives
rise to Microsatellite Instability
Loss of MSH2 function increases mutation frequencies
by two to three magnitudes
MSH2
MSH6 MSH2
MutSα
Cytoplasm
Nuclear Envelope
MSH3 MSH2
Larger
insertion/deletion
loops
MutSβ
Base mismatch repair
and small
insertion/deletion
loops
Lynch Syndrome
HPNCC is another
term for MSH2
Hereditary Nonpolyposis Colorectal Cancer
(HNPCC)
MSH2 and HNPCC
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.
References
• Ls Gentics HPNCC. (n.d.). Retrieved March 31, 2015,
from http://www.lynch-syndromeuk.org/ls_genetics_.html
• MSH2 gene. (n.d.). Retrieved March 31, 2015, from
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
• Tomasetti, C. (2015). Variation in cancer risk among
tissues can be explained by the number of stem cell
divisions. Science, 347(6217), 78-81.