A genetic model for colorectal tumorigenesis

  title={A genetic model for colorectal tumorigenesis},
  author={Eric R. Fearon and Bert Vogelstein},

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Genetic alterations in the adenoma–carcinoma sequence
Several different genetic alterations were identified that occur during colorectal tumorigenesis, including the gene dcc, which has significant sequence similarity to neural cell adhesion molecules and other related cell‐surface glycoproteins and may have important functions in mediating cell growth and differentiation.
Mutator phenotype may be required for multistage carcinogenesis.
  • L. Loeb
  • Biology, Medicine
    Cancer research
  • 1991
It is argued that an early step in tumor progression is one that induces a mutator phenotype, and an increased mutation rate in tumors could be the basis for the multiple mutations that characterize many cancers.
Genetic pathways in colorectal cancer
How tumour development can occur as Darwinian evolution through selection of advantageous somatic mutations and the non‐random nature of mutation selection gives rise to genetic pathways of tumorigenesis is discussed.
Genetic Alterations in Colon Cancer
Human colon cancer has proven to be an excellent model system for studying the development of malignant disease in humans and is believed to involve the occurrence of four to six separate genetic changes over a period of years.
Molecular Pathogenesis of Endometrial Cancer
A genetic model for tumorigenesis has been proposed that illustrates the multistep process in the development of colorectal cancer and it is likely that this model can be applied to the study of other human neoplasms in which tumor development is less well defined, such as endometrial carcinoma.
Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells
Experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant Transformation, and Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.
Molecular markers of heterogeneity in colorectal cancers and adenomas
This study will attempt to review the major advances in the understanding of the genetic basis of colorectal carcinogenesis by reviewing the major improvements made since Fearon and Vogelstein (1990).
Mechanism of carcinogenesis in familial tumors
The tumor phenotype from patients with hereditary nonpolyposis colorectal cancer is demonstrated to be microsatellite instability positive, and three major genes are closely related to the cell cycle and tumorigenesis.
Multiple Steps in the in vitro Immortalisation and Neoplastic Conversion of Human Colonic Epithelial Cells
To establish an in vitro model for tumour progression by transforming premalignant human colonic adenoma cells to the malignant phenotype, isolated epithelial cell lines from sporadic and FAP adenomas are isolated.


Chromosome 5 allele loss in human colorectal carcinomas
Examination of sporadic colorectal adenocarcinomas for loss of alleles on chromosome 5 parallels the assignment of the FAP gene to chromosome 5 and suggests that becoming recessive for this gene may be a critical step in the progression of a relatively high proportion of coloreCTal cancers.
Mutations in human breast cancer: an overview.
Eight mutations have been identified, including amplification of c-myc, c-erbB2, and int-2, as well as loss of heterozygosity on five chromosomes, which are thought to unmask recessive mutations of tumor-suppressor genes.
Clonal analysis of human colorectal tumors.
Data support a monoclonal origin for colorectal neoplasms, and suggest that a gene on the short arm of chromosome 17 may be associated with progression from the benign to the malignant state.
Expression of the myc gene family in different stages of human colorectal cancer.
The c-myc gene was overexpressed in tumors and polyps, but in most cases the level of overexpression was modest and a single case of adenocarcinoma showed an approximately 30-fold increase in thelevel of N- myc mRNA without gene amplification.
Allelotype of colorectal carcinomas.
In addition to its implications concerning the genetic events underlying tumorigenesis, tumor allelotype may provide a molecular tool for improved estimation of prognosis in patients with colorectal cancer.
Localization of the gene for familial adenomatous polyposis on chromosome 5
It is shown that the FAP gene is on chromosome 5, most probably near bands 5q21–q22, and that the same gene may be involved in both familial and non-familial cases of a given tumour.
The clonal evolution of tumor cell populations.
Each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment, which should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.
Mutations in the p53 gene occur in diverse human tumour types
It is suggested that most tumours with allelic deletions of chromosome 17p contain p53 point mutations resulting in amino-acid substitutions, and p53 gene mutations are clustered in four 'hot-spots' which exactly coincide with the four most highly conserved regions of the gene.
Genetics of cancer predisposition.
Evidence is consolidated from familial, epidemiológica!, cytogenetic, and molecular ge netic studies which support the notion that cancer is a pro foundly genetic disease and which help explain the seeming paradoxes.
Abnormal methylation of the calcitonin gene in human colonic neoplasms.
The data provide further evidence that regional increases in DNA methylation, like gene hypomethylation, occur in benign colonic neoplasms prior to malignant transformation and that the calcitonin gene hypermethylation may be inherent to cells which are initially selected for growth in culture or are capable of prolonged survival under culture conditions.