Clinicopathologic Characteristics, Cpg Island Methylator Phenotype, And BRAF Mutations in Microsatellite-Stable Colorectal Cancers Without Chromosomal Instability (Report)

Clinicopathologic Characteristics, Cpg Island Methylator Phenotype, And BRAF Mutations in Microsatellite-Stable Colorectal Cancers Without Chromosomal Instability (Report)

Colorectal cancer is characterized by a multistep progression of genetic errors that lead to derangement of epithelial growth and differentiation. (1) Two apparently distinct pathways of genomic instability have been implicated in carcinogenesis. Microsatellite instability plays a role in colorectal carcinomas arising in the setting of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) and in 10% to 20% of sporadic colorectal cancers. (2-6) In the hereditary setting, the phenomenon reflects accumulated errors in DNA microsatellite repeat sequences following inactivation of a DNA-mismatch repair enzyme, like hMLHl and hMSH2 via mutation, whereas inactivation of hMLHl occurs by hypermethylation of its promoter region in sporadic cancers. (2,3,7) Chromosomal instability is characterized by allelic gains or losses at multiple sites in the genome, leading to inactivation of putative tumor suppressor genes. The principal loci include 5q (APC), 17p (TP53), 18q (DCC, SMAD 2, and SMAD4), and 8q (no candidate gene identified). (8-11) Less commonly, chromosomal losses at 1p, 2p, 3p, 6q, 14q, and 15q, and gains involving 20q, 13q, 7q, and 8q are observed. (10-12)

Clinicopathologic Characteristics, Cpg Island Methylator Phenotype, And BRAF Mutations in Microsatellite-Stable Colorectal Cancers Without Chromosomal Instability (Report)

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