Hereditary nonpolyposis colon cancer

PMSl). The DNA located between the nick and the mismatch is removed by 3 to 5 or 5 to 3 exonucleases depending on whether the nick is 3 or 5 to the mismatch. The gap is then filled by DNA Pol III in E. coli (Fig. 10) by DNA Pol 5 in humans and is ligated. Mismatch repair increases the spontaneous mutation rate in E. coli and yeast. Humans defective in mismatch repair exhibit a cancer-prone syndrome called hereditary nonpolyposis colon cancer (HNPCC), and sporadic mutations of mismatch repair genes are also associated with up to 50% of all human cancers (42 4). 

R. Fishel, M.K. Lescoe, M.R.S. Rao, N.G Copeland, N.A. Jenkins, J. Garber, M. Kane, and R. Kolodner. 1993. The human mutator gene homologTV75772 and its association with hereditary nonpolyposis colon cancer Cell 75 1027-1038. (PubMed)... 

Burke W, Peterson G, Lynch P, Botkin J, Daly M, Garber J, et al. Recommendations for follow-up care of individuals with inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Cancer Genetics Studies Consortium. JAMA 1997 277 915-9. 

Jenkins NA, Garber J, et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. CeU 1993 75 1027-38. 

Several human DNA mismatch repair genes are associated with hereditary nonpolyposis colon cancer (HNPCC). One of these mismatch repair genes (hMSH2) is located on the short arm of chromosome 2 others are located on chromosome 3. Defects in any of these DNA repair genes predispose individuals to colon cancer as well as to other cancers. 

Patients with hereditary nonpolyposis colon cancer [HNPCC (114500)] have genes with microsatellite instability, that is, many regions containing abnormal, small loops of unpaired DNA. This is a result of a mutation affecting... 

Women with or at risk for hereditary nonpolyposis colon cancer should begin annual endometrial biopsy starting at age 35. To include examination for cancers of the mouth, thyroid, testicles, skin, lymph nodes, and ovaries, as well as health counseling about tobacco, sun exposure, diet and nutrition, risk factors, sexual practices, and environmental and occupational exposures. From The American Cancer Society. ... 

Endometrium Hereditary nonpolyposis colon cancer (HNPCC)... 

FIGURE 14.22 High and low magnification of an invasive cecal adenocarcinoma from a 46-year-old patient with hereditary nonpolyposis colon cancer syndrome (Lynch syndrome). Neoplastic cell nuclei are completely devoid of MLH2 immunoreactivity, whereas cell nuclei of the surrounding stromal cells stain strongly. Only the complete absence of nuclear staining should be interpreted as a marker of a mismatch repair enzyme defect. 

As discussed earlier in this chapter, Lynch syndrome or hereditary nonpolyposis colon cancer syndrome (HNPCC) is a cancer predisposition syndrome caused by mutation of a mismatch repair gene. Immunohistochemistry can be used to screen for mutations in... 

Mismatch repair is required to remove incorrect nucleotides from mismatched base pairs in newly synthesized DNA. It is critical that the repair proteins be able to distinguish between the template and nascent DNA strands to avoid "correcting" the wrong nucleotide. In E. coli, the nascent DNA strand is transiently unmethylated at adenines in the sequence GATC. Mutations in the human homologues (hMSH2 and hMLHl) of bacterial-mismatch repair enzymes have been associated with hereditary nonpolyposis colon cancer. 

Hereditary nonpolyposis colon cancer family syndrome... 

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