Cancer As A Genetic Disease

The characteristic properties of cancer cells (^1.3) are to a large extent the consequences of genetic changes in the tumor cells. Indeed, genomic instability is one of the properties defining cancer and the aberrant structure of the nucleus seen in many cancer cells is an obvious morphological consequence of their altered genome. It is plausible that every cancer cell contains structural or numerical alterations of its genome. The number of alterations is not precisely known, and certainly varies with cancer type and stage of progression. Systematic DNA sequencing has yielded estimates of hundreds to thousands of point mutations in some tumors. Screening by arbitrary PCR has suggested an even higher number of alterations for some cancers. Certainly, 20 or more chromosomal aberrations detectable by cytogenetic techniques are not unusual in an advanced carcinoma.

It is therefore very appropriate to regard cancer as a genetic disease. Still, a few points must be kept in mind:

(1) Only a minority of cancers are caused by mutations inherited in the germline. Rather, the vast majority of genetic alterations found in cancers develop during the life of a patient in somatic cells. Thus, cancer is almost always a disease caused by 'somatic mutations'. Even in cancers which are passed on over several generations in a family, the initial inherited mutations are complemented by additional somatic mutations. Likewise, cancers arising in young children or adolescents are often caused by mutations originating de novo in their parents' germ cells or during intra-uterine development. A typical cancer of this kind is Wilms tumor (^11), but similar circumstances apply to testicular cancer and certain childhood leukemias.

(2) The relationship between mutant genotype and disease phenotype is not straightforward in cancer, which per se is not so unusual for genetic diseases. However, in cancer the relationship is extremely complex. Cancer cells as a rule contain many different mutations which each may contribute to various extents to the properties of the tumor.

(3) Not all properties of cancer cells may result from genetic defects. Many stable changes in cancer cells may be set up by regulatory loops without alterations in the sequence or the amount of DNA. Such changes are designated as 'epigenetic' (^■8). They can occur within a cancer cell or concern its interaction with other cell types (^8).

10 Ways To Fight Off Cancer

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