| Entry |
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| Name |
Colorectal cancer
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| Description |
Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes (TSG). Two major mechanisms of genomic instability have been identified in sporadic CRC progression. The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of oncogenes such as K-ras and inactivation of TSG such as p53, DCC/Smad4, and APC. The second, known as microsatellite instability (MSI), results from inactivation of the DNA mismatch repair genes MLH1 and/or MSH2 by hypermethylation of their promoter, and secondary mutation of genes with coding microsatellites, such as transforming growth factor receptor II (TGF-RII) and BAX. Hereditary syndromes have germline mutations in specific genes (mutation in the tumour suppressor gene APC on chromosome 5q in FAP, mutated DNA mismatch repair genes in HNPCC).
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| Class |
Human Diseases; Cancers
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| Pathway map |
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| Disease |
| Colorectal cancer | | Oligodontia-colorectal cancer syndrome | | Mismatch repair deficiency | | Juvenile polyposis syndrome | | Familial adenomatous polyposis |
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| Reference |
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| Authors |
Grady WM. |
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| Title |
Genomic instability and colon cancer. |
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| Journal |
Cancer Metastasis Rev 23:11-27 (2004) |
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| Reference |
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| Authors |
Soreide K, Janssen EA, Soiland H, Korner H, Baak JP. |
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| Title |
Microsatellite instability in colorectal cancer. |
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| Journal |
Br J Surg 93:395-406 (2006) |
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| Reference |
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| Authors |
Anwar S, Hall C, White J, Deakin M, Farrell W, Elder JB. |
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| Title |
Hereditary non-polyposis colorectal cancer: an updated review. |
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| Journal |
Eur J Surg Oncol 26:635-45 (2000) |
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| Reference |
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| Authors |
Takayama T, Miyanishi K, Hayashi T, Sato Y, Niitsu Y. |
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| Title |
Colorectal cancer: genetics of development and metastasis. |
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| Journal |
J Gastroenterol 41:185-92 (2006) |
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| Reference |
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| Authors |
Lynch HT, de la Chapelle A. |
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| Title |
Hereditary colorectal cancer. |
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| Journal |
N Engl J Med 348:919-32 (2003) |
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| Reference |
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| Authors |
Rajagopalan H, Nowak MA, Vogelstein B, Lengauer C. |
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| Title |
The significance of unstable chromosomes in colorectal cancer. |
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| Journal |
Nat Rev Cancer 3:695-701 (2003) |
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| Reference |
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| Authors |
Behrens J. |
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| Title |
Cadherins and catenins: role in signal transduction and tumor progression. |
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| Journal |
Cancer Metastasis Rev 18:15-30 (1999) |
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| Reference |
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| Authors |
Behrens J. |
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| Title |
The role of the Wnt signalling pathway in colorectal tumorigenesis. |
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| Journal |
Biochem Soc Trans 33:672-5 (2005) |
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| Reference |
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| Authors |
Behrens J, Lustig B. |
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| Title |
The Wnt connection to tumorigenesis. |
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| Journal |
Int J Dev Biol 48:477-87 (2004) |
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| Reference |
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| Authors |
Polakis P. |
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| Title |
The adenomatous polyposis coli (APC) tumor suppressor. |
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| Journal |
Biochim Biophys Acta 1332:F127-47 (1997) |
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| Reference |
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| Authors |
Janssen KP. |
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| Title |
Murine models of colorectal cancer: studying the role of oncogenic K-ras. |
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| Journal |
Cell Mol Life Sci 60:495-506 (2003) |
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| Reference |
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| Authors |
Adjei AA. |
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| Title |
Blocking oncogenic Ras signaling for cancer therapy. |
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| Journal |
J Natl Cancer Inst 93:1062-74 (2001) |
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| Reference |
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| Authors |
Arakawa H. |
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Netrin-1 and its receptors in tumorigenesis. |
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| Journal |
Nat Rev Cancer 4:978-87 (2004) |
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| Reference |
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| Authors |
Mehlen P, Fearon ER. |
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| Title |
Role of the dependence receptor DCC in colorectal cancer pathogenesis. |
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| Journal |
J Clin Oncol 22:3420-8 (2004) |
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| Reference |
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| Authors |
Peltomaki P. |
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| Title |
DNA mismatch repair and cancer. |
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| Journal |
Mutat Res 488:77-85 (2001) |
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| Reference |
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| Authors |
Li F, Cao Y, Townsend CM Jr, Ko TC. |
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| Title |
TGF-beta signaling in colon cancer cells. |
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| Journal |
World J Surg 29:306-11 (2005) |
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| Reference |
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| Authors |
Roman C, Saha D, Beauchamp R. |
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| Title |
TGF-beta and colorectal carcinogenesis. |
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| Journal |
Microsc Res Tech 52:450-7 (2001) |
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| Reference |
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| Authors |
Watson AJ. |
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| Title |
An overview of apoptosis and the prevention of colorectal cancer. |
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| Journal |
Crit Rev Oncol Hematol 57:107-21 (2006) |
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| Reference |
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| Authors |
Watson AJ. |
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| Title |
Apoptosis and colorectal cancer. |
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| Journal |
Gut 53:1701-9 (2004) |
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| Reference |
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| Authors |
Houlston RS. |
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| Title |
What we could do now: molecular pathology of colorectal cancer. |
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| Journal |
Mol Pathol 54:206-14 (2001) |
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| KO pathway |
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