Two genetic hits (more or less) to cancer

@article{Knudson2001TwoGH,
  title={Two genetic hits (more or less) to cancer},
  author={Alfred G. Knudson},
  journal={Nature Reviews Cancer},
  year={2001},
  volume={1},
  pages={157-162}
}
  • A. Knudson
  • Published 1 November 2001
  • Biology
  • Nature Reviews Cancer
Most cancers have many chromosomal abnormalities, both in number and in structure, whereas some show only a single aberration. In the era before molecular biology, cancer researchers, studying both human and animal cancers, proposed that a small number of events was needed for carcinogenesis. Evidence from the recent molecular era also indicates that cancers can arise from small numbers of events that affect common cell birth and death processes. 

Chromosomal abnormalities in cancer.

The authors point out that some of the chromosomal abnormalities have revealed targets for cancer treatment, and others have clinical application in the diagnosis of certain types of neoplasms and in the formulation of a prognosis.

The significance of unstable chromosomes in colorectal cancer

Experimental and theoretical evidence for the initiation of chromosomal instability in very early colorectal cancers is explored, and the role that chromosomal stability could have in coloreCTal tumorigenesis is reflected on.

Molecular Models of Cancer Development

Cause and metabolic pathways of oncogenesis and the influence of the environmental factors on cancer (Epigenetics) and a new paradigm related to Retinoblastoma, a hereditary human malignancy which may involve orbit secondarily, is offered.

Aneuploidy and cancer

A growing body of evidence suggests that aneuploidy is often caused by a particular type of genetic instability, called chromosomal instability, which may reflect defects in mitotic segregation in cancer cells.

The Role of Chromosome Deletions in Human Cancers.

This chapter will focus on the latest studies on the functions of chromosome deletions in human cancers, especially hematopoietic malignancies and try to persuade the readers that these chromosome alterations could play significant roles in the genesis and drug responses of human cancers.

Sequence Mutations of Genes Pertaining to Malignancy in Cancer

This review will describe sequence mutations of several cancer-related genes and discuss their functional implications in cancer, and introduce the on-line resources for accessing and analyzing sequence mutations in cancer.

Only three driver gene mutations are required for the development of lung and colorectal cancers

It is shown that only three sequential mutations are required to develop lung and colon adenocarcinomas, a number that is lower than what is typically thought to be required for the formation of cancers of these and other organs.

Genomic instability — the engine of tumorigenesis?

T theoretical analysis and experimental data from sporadic colorectal tumours provide little general evidence of genomic instability in early lesions, raising the question of whether or not genomic instability is necessary for driving tumour growth, andWhether or not it is the usual initiating event in tumorigenesis.

CIN-ful cancers

This work believes that aneuploidy in cancers is the result of chromosomal instability, a process in which dividing cancer cells segregate their chromosomes with decreased fidelity.

A History of Cancer Research: Tumor Suppressor Genes.

  • J. Lipsick
  • Biology
    Cold Spring Harbor perspectives in biology
  • 2020
In this excerpt from his forthcoming book on the history of cancer research, Joe Lipsick looks back at the discovery of tumor suppressor genes, covering the early work on cell fusion by Henry Harris, Knudson's two-hit hypothesis, the genetic mapping studies that first identified the RB gene, and subsequent work on silencing.
...

References

SHOWING 1-10 OF 61 REFERENCES

Genetic instabilities in human cancers

There is now evidence that most cancers may indeed be genetically unstable, but that the instability exists at two distinct levels, and recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis.

The onset and extent of genomic instability in sporadic colorectal tumor progression.

These results support the model of genomic instability being a cause rather than an effect of malignancy, facilitating vastly accelerated somatic cell evolution, with the observed orderly steps of the colon cancer progression pathway reflecting the consequences of natural selection.

Cancer genetics: from Boveri and Mendel to microarrays

The human genome has now been sequenced, a century after the re-discovery of Mendel's Laws, and the publication of Theodor Boveri's chromosomal theory of heredity. Tracing the historical landmarks of

Model for the incidence of embryonal cancers: application to retinoblastoma.

  • H. HethcoteA. Knudson
  • Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1978
A quantitative model using the Poisson distribution is developed for ages at diagnosis for hereditary and nonhereditary cases, which relates age-specific incidence data explicitly to the number of divisions of embryonal cells and to rates of somatic mutations per cell division.

Evidence that genetic instability occurs at an early stage of colorectal tumorigenesis.

It is suggested that chromosomal instability occurs very early during colorectal neoplasia, even in very small tumors, and newly developed methods for assessing AI in complex cell populations are used.

Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.

Germ line p53 mutations have been detected in all five LFS families analyzed and can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.

A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma

The isolation of a complementary DNA segment that detects a chromosomal segment having the properties of the gene at this locus is described, which is expressed in many tumour types, but no RNA transcript has been found in retinoblastomas and osteosarcomas.

Mutation and Human Cancer

Mutator phenotypes in human colorectal carcinoma cell lines.

The data suggest that the mutatw phenotypes in the colorectal carcinoma cell lines could be the consequence of mutator genes affecting different repair or error-avoidance pathways.
...