Abstract
This chapter summarizes genetic predisposition to cancer, the various kinds of genetic changes in cancer cells, and introduces some of the mechanisms causing them. Cancer cells typically contain multiple alterations in their genomes, including mutations altering the base sequence of their DNA, gene copy number variation, and numerical and structural chromosomal alterations. Most genomic alterations are acquired by mutations in somatic cells. The type and number of genetic changes and the extent of genomic instability vary widely between cancers. Germline mutations underlie familial cancer syndromes that can be inherited in a recessive or a dominant fashion. They increase the lifetime risk for cancer several fold, but are relatively rare. In contrast, inherited variations in a large number of genes that weakly or moderately influence cancer risk are highly prevalent. Genetic changes in more than 700 different cancer genes can cause cancers. Two important classes of cancer genes are oncogenes and tumor suppressors. Most cancer genes encode proteins, but regulatory RNAs may also contribute. Typically, alterations in several genes are required for cancer development and progression. Tumor viruses introduce extra genetic material, in particular viral oncogenes, but may also deregulate cellular genes and elicit genomic instability. Genetic changes in cancers are compounded or supplemented by epigenetic deregulation.
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Notes
- 1.
The N-terminal PTC domain mediates constitutive homodimerization of the fusion protein leading to ligand-independent activation of the RET tyrosine kinase, see Sect. 4.4.
- 2.
Extrachromosomal circular DNA can be generated by several processes, including recombination, breakage-fusion-bridge cycles and chromothripsis.
- 3.
The risk of GSTM1−/− smokers to contract bladder cancer, e.g., is about 1.5-fold elevated. This is a typical magnitude for polymorphisms, the relative risk factor conferred by different alleles of a polymorphic gene often varies between 0.5 and 2.
- 4.
This term is not used consistently in the literature; one alternative designation is “enablers.”
- 5.
Where the earliest “truncal” mutations should be present in 100% of the cancer cells.
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Schulz, W.A. (2023). Cancer Genetics. In: Molecular Biology of Human Cancers. Springer, Cham. https://doi.org/10.1007/978-3-031-16286-2_2
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