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Review
. 2009 Dec 17;361(25):2449-60.
doi: 10.1056/NEJMra0804588.

Molecular origins of cancer: Molecular basis of colorectal cancer

Sanford D Markowitz  1 , Monica M Bertagnolli
Affiliations
Review

Molecular origins of cancer: Molecular basis of colorectal cancer

Sanford D Markowitz et al. N Engl J Med. .
No abstract available

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Figures

Figure 1
Figure 1. Multifactorial Colorectal Carcinogenesis
The molecular events that drive the initiation, promotion, and progression of colorectal cancer occur on many interrelated levels. This dynamic process involves interactions among environmental influences, germ-line factors dictating individual cancer susceptibility, and accumulated somatic changes in the colorectal epithelium.
Figure 2
Figure 2. Genes and Growth Factor Pathways That Drive the Progression of Colorectal Cancer.
In the progression of colon cancer, genetic alterations target the genes that are identified at the top of the diagram. The microsatellite instability (MSI) pathway is initiated by mismatch-repair (MMR) gene mutation or by aberrant MLH1 methylation and is further associated with downstream mutations in TGFBR2 and BAX. Aberrant MLH1 methylation and BRAF mutation are each associated with the serratedadenoma pathway. The question mark indicates that genetic or epigenetic changes specific to metastatic progression have not been identified. Key growth factor pathways that are altered during colon neoplasia are shown at the bottom of the diagram. CIN denotes chromosomal instability, EGFR epidermal growth factor receptor, 15-PGDH 15-prostaglandin dehydrogenase, and TGF-β transforming growth factor β.
Figure 3
Figure 3. Genetic Instability Pathways That Drive Colon Neoplasias
Shown are the overlapping relationships that define the major pathways of genomic instability in colon cancers: chromosomal instability, microsatellite instability caused by defects in DNA mismatch-repair genes that are either inherited as germ-line defects (e.g., in hereditary nonpolyposis colon cancer) or somatically acquired (e.g., by aberrant methylation and epigenetic silencing of MLH1), and the CpG island methylator phenotype.
See this image and copyright information in PMC

Comment in

  • Molecular basis of colorectal cancer.
    Kouzminova N, Lu T, Lin AY. Kouzminova N, et al. N Engl J Med. 2010 Apr 1;362(13):1245-6; author reply 1246-7. doi: 10.1056/NEJMc1000949. N Engl J Med. 2010. PMID: 20357292 No abstract available.
  • Molecular basis of colorectal cancer.
    Batistatou A, Charalabopoulos A, Charalabopoulos K. Batistatou A, et al. N Engl J Med. 2010 Apr 1;362(13):1246; author reply 1246-7. N Engl J Med. 2010. PMID: 20364460 No abstract available.
  • Molecular basis of colorectal cancer.
    Purnak T, Ozaslan E, Efe C. Purnak T, et al. N Engl J Med. 2010 Apr 1;362(13):1246; author reply 1246-7. N Engl J Med. 2010. PMID: 20364461 No abstract available.

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