ADRBK1, AKT1, APC, APPL1, ARRB1, AXIN2, BAX, BCL2L1, BIRC5, BRAF, CASP3, CASP9, CCND1, CCND2, CDH1, CDKN1A, CTNNB1, DCC, DVL1, E2F4, EGF, EGFR, FZD1, GNAS, GNB3, GRB2, GSK3B, IFNG, IFNGR1, IL6, IL6R, JAK1, KRAS, LEF1, LRP5, LRP6, MAP2K1, MAP2K2, MAP2K4, MAP2K6, MAPK1, MAPK3, MLH1, MMP1, MMP14, MMP2, MMP7, MMP9, MSH2, M...SH6, MYC, NFKB1, NFKB2, NOS2, PIK3CA, PIK3CB, PIK3R1, PIK3R2, PRKACA, PRKAR1A, PTGER2, PTGER4, PTGS2, REL, RELA, RELB, SMAD2, SMAD3, SMAD4, SOS1, SRC, STAT1, STAT3, TCF3, TCF4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TLR2, TLR3, TLR4, TLR7, TLR9, TNF, TNFRSF1A, TP53, VEGFA, WNT1, WNT3A, WNT5A
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Colorectal cancer represents a relatively well-characterized tumorigenesis paradigm and colorectal carcinoma is one of the leading causes of cancer-related death. Colorectal cancer results from the accumulation of genetic alterations. Genomic instability ...creates a permissive state in which a potential cancer cell is allowed to acquire enough mutations to become a cancer cell. Several forms of genomic instability are common in colon cancer: MSI (Microsatellite Instability), CIN (Chromosome Instability), and chromosome translocations. MSI occurs in approximately 15% of colon cancers and results from inactivation of the MMR (Mismatch Repair) system secondary to either MMR gene mutations or hypermethylation of MMR gene promoters. It promotes tumorigenesis by generating mutations in target genes that possess coding microsatellite repeats. CIN occurs in most other colon cancers and leads to a different pattern of gene alterations that culminate in tumor formation. It seems to result from mutations in genes that control mitosis, DNA damage repair, centrosome structure and function, and other fundamental processes in DNA replication. In general the genetic alterations in colorectal cancer progression are determined by one of two separate and distinct underlying pathways of genomic instability. The first pathway, CNI, is characterized by allelic losses, LOH (Loss of Heterozygosity), aneuploidy, diploidy, polyploidy, telomere shortening and methylation. The second pathway, MSI, is characterized by an abundance of subtle DNA mutations. Although the genes causing chromosomal instability remain unknown, MSI is caused by inactivation of a DNA mismatch repair gene predominantly MLH1 (MutL Homolog-1) or MSH2. Major environmental factors, which influence such gene alternations, include invasion by pathogens (bacterial and viral infections), toxins, stress, polyamines, inflammation, and generation of ROS (Reactive Oxygen Species). The MSI and CIN mutations mainly alter the WNT (Wingless-Type MMTV Integration Site Family), CdhE (Epithelial Cadherin), Prostaglandin, EGFR (Epidermal Growth Factor Receptor), TGF-BetaR (Transforming Growth Factor-Beta Receptor) and DCC (Deleted in Colorectal Carcinoma) signaling routes to facilitate proliferation of colorectal carcinoma. These signaling routes act as check gates in the development of human neoplasia.
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