A genetic model for colorectal tumorigenesis

@article{Fearon1990AGM,
  title={A genetic model for colorectal tumorigenesis},
  author={Eric R. Fearon and Bert Vogelstein},
  journal={Cell},
  year={1990},
  volume={61},
  pages={759-767}
}

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References

SHOWING 1-10 OF 78 REFERENCES
Chromosome 5 allele loss in human colorectal carcinomas
TLDR
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.
TLDR
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.
TLDR
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.
TLDR
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.
TLDR
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
TLDR
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.
TLDR
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
TLDR
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.
TLDR
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.
TLDR
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.
...
...