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"Name": "Storage Conditions (Product)",
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{
"Name": "Background Information",
"Value": "Microsatellite instability (MSI) is characterized by genome-wide alterations in short, repetitive DNA sequences. It is caused by defects in the nucleotide mismatch repair (MMR) system
1. Biologically, defective MMR results in a general increase in the mutation rate and the development of a “mutator phenotype”
1,2,3,4,5. In colorectal cancer (CRC), high-level MSI was first described in tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC). In about 70% of cases, the HNPCC syndrome develops as a result of an inherited germline mutation of one allele, followed by a somatic mutation of the other allele in one of several mismatch repair genes: hMSH2, hMLH1, hPMS1, hPMS2, hMSH6,and hMLH3
2,6. 95% percent of the mutations occur in hMSH2 or hMLH1
2,6,7. Most colorectal carcinomas are thought to be of the chromosomal instable (CIN) or microsatellite stable (MSS) genotype. However, approximately 15% are thought to be of the MSI genotype, of which the HNPCC cases represent less than one-third
2,7. The MSS and MSI tumors also seem to differ in clinicopathologic features. The MSI tumors are more often located in the proximal colon and may be synchronous. On histologic examination, they are more often mucinous or poorly differentiated. The patients with MSI-type colorectal carcinomas are generally thought to have a better prognosis than patients with MSS-type colorectal carcinomas. On the other hand, MSS tumors are more often located in the distal colon and represent typical adenocarcinomas
6. Although the results published so far have been conflicting, some studies suggest that patients with MSS-type colorectal carcinomas seem to have a greater benefitfrom adjuvant chemotherapy (with 5-FU) than patients with MSI-type colorectal carcinomas. In contrast, there is some evidence that MSI-CRCs respond better to CPT-11 (irrinotecan) than MSS-CRCs
6.
1. Gologan A, et al. Microsatellite Instability and DNA Mismatch Repair Deficiency Testing in Hereditary and Sporadic Gastrointestinal Cancers. Clin Lab Med. 2005;25:179-96. Review.
2. Lagerstedt Robinson K, Liu T, Vandrovcova J, Halvarsson B, Clendenning M, Frebourg T, Papadopoulos N, Kinzler KW, Vogelstein B, Peltomäki P, Kolodner RD,Nilbert M, Lindblom A. Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics. J Natl Cancer Inst. 200;99:291-9.
3. Hendriks YM, Jagmohan-Changur S, van der Klift HM, Morreau H, van Puijenbroek M, Tops C, van Os T, Wagner A, Ausems MG, Gomez E, Breuning MH, Bröcker-Vriends AH, Vasen HF, Wijnen JT. Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome). Gastroenterology. 2006;130:312-22.
4. Truninger K, Menigatti M, Luz J, Russell A, Haider R, Gebbers JO, Bannwart F,Yurtsever H, Neuweiler J, Riehle HM, Cattaruzza MS, Heinimann K, Schär P, Jiricny J, Marra G. Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer. Gastroenterology. 2005;128:1160-71.
5. Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 2005;352:1851-60.
6. Warusavitarne J, Schnitzler M. The role of chemotherapy in microsatellite unstable (MSI-H) colorectal cancer. In J Colorectal Dis (2007) 22: 739-748.
7. Gill S, Lindor NM, Burgart LJ, Smalley R, Leontovich O, French AJ, GoldbergRM, Sargent DJ, Jass JR, Hopper JL, Jenkins MA, Young J, Barker MA, Walsh MD,Ruszkiewicz AR, Thibodeau SN. Isolated loss of PMS2 expression in colorectal cancers: frequency, patient age, and familial aggregation. Clin Cancer Res. 2005;11:6466.",
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