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The Genetics of Colorectal Cancer

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Metastasis of Colorectal Cancer

Part of the book series: Cancer Metastasis - Biology and Treatment ((CMBT,volume 14))

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Abstract

Colorectal cancer arises as the result of the accumulation of genetic alterations (including gene mutations and amplification) and epigenetic modifications (such as aberrant DNA methylation and chromatin modifications) that transform normal colonic epithelial cells into adenocarcinoma cells. Loss of genomic stability and the resulting genetic changes appears to be a crucial molecular and pathogenic step that occurs early in the tumourigenic process and permits a sufficient number of alterations in tumour suppressor genes and oncogenes to accumulate in a clone of cells to result in their eventual transformation into cancer. Substantial progress has been made recently concerning potential causes of chromosomal instability in colorectal cancer and in determining the effects of the various forms of genomic instability on the biological and clinical behavior of colon tumours. Furthermore, progress has been made in terms of understanding the specific signalling pathways that are frequently deregulated in colorectal cancers. Although the discovery of genes involved in colorectal cancer metastasis remains a challenge, advancements in our understanding of the molecular genetics of this process have occurred, both with traditional familial/linkage studies and also utilizing state-of-the-art genome-wide searches. The evaluation of the cause and role of the genetic events involved in colorectal cancer formation has the potential to yield more effective prevention and treatment strategies for this disease.

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Abbreviations

ACVR2:

Activin receptor type II

BAX:

Bcl-2–associated X protein

BER:

Base Excision Repair

BMPs:

Bone Morphogenetic Proteins

BRAF:

V-raf murine sarcoma viral oncogene homolog B1

CCDS:

Consensus coding sequences

CDC4:

Cell division cycle 4

Cdk4:

Cyclin-dependent kinase 4

CIMP:

CpG island methylator phenotype

CIN:

Microsatellite instability

CpG:

Cytosine-phosphate-guanine

CRC:

Colorectal cancer

CtBP1:

C-terminal-binding protein 1

CTNNB1:

β-catenin encoding gene

EB1:

End binding protein

FAP:

Familial adenomatous polyposis

Fbw7:

F-box/WD repeat-containing protein 7

FOXO:

Forkhead box, sub-group O

EGFR:

Epidermal growth factor receptor

GDFs:

Growth and differentiation factors

GSK-3β:

Glycogen synthase kinase-3β

hDLG:

Homologue of Discs Large

HNPCC:

Hereditary nonpolyposis colon cancer

HR:

Hazard ratio

JPS:

Juvenile polyposis

LOH:

Loss of heterozygosity

MAP:

MYH-Associated adenomatous polyposis syndrome

MAPK:

Mitogen-activated protein kinase

MKK4/JNKK1:

Mitogen activated protein-kinase kinase-4

MSH:

Muts homolog, colon cancer, nonpolyposis type 1 (E. coli)

MLH1:

MutL homolog 1, colon cancer, nonpolyposis type 2 (MLH1)

MMR:

DNA Mismatch Repair

MRE11:

Murein formation gene cluster E

MSI:

Microsatellite instability

MSS:

Microsatellite stable

MTHF1:

Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1

MYC:

v-myc myelocytomatosis viral oncogene homolog

MYH:

MutY human homologue

MYLK2:

Myosin light-chain kinase-2

OGG1:

8-Oxoguanine DNA glycosylase

PAK4:

p21-activated kinase 4

PCNA:

Proliferating cell nuclear antigen

PDK1:

Phosphoinositide-dependent protein kinase-1

PI3K/AKT:

Phosphatidyl inositol 3 kinase/v-akt murine thymoma viral oncogene homologue 1

PMS2:

Postmeiotic segregation increased 2

PRL-3:

Metastasis-associated phosphatase of regenerating liver-3

PTEN:

Phosphatase and tensin homolog deleted on chromosome 10

PTK:

Protein tyrosine kinase

PTP:

Phosphatase

RFC:

Replication factor C

RPA:

Replication protein A

SNP:

Single nucleotide polymorphisms

SFRP:

Secreted frizzled-related protein

TCF/Lef:

T-cell factor/lymphoid enhancing factor

TGFβ:

Transforming growth factor β

TGFBR2:

TGF-β receptor type II

TP53:

Tumor protein 53

WNT:

Wingless/Wnt

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    Andrew M. Kaz & William M. Grady

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Editors and Affiliations

  1. Rosalind & Morris Goodman Cancer, Research Centre, McGill University, Promenade Sir William Osler 3655, Montreal, H3G 1Y6, Canada

    Nicole Beauchemin

  2. Hôpital L’Hôtel-Dieu de Québec, Centre de Recherche en Cancérologie, Université Laval, rue McMahon 9, Quebec, G1R 2J6, Canada

    Jacques Huot

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Kaz, A.M., Grady, W.M. (2010). The Genetics of Colorectal Cancer. In: Beauchemin, N., Huot, J. (eds) Metastasis of Colorectal Cancer. Cancer Metastasis - Biology and Treatment, vol 14. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8833-8_3

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