News tagged with carcinogenesis

Carcinogenesis or oncogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells. It is characterized by a progression of changes on cellular and genetic level that ultimately reprogram a cell to undergo uncontrolled cell division, thus forming a malignant mass.

Cell division is a physiological process that occurs in almost all tissues and under many circumstances. Under normal circumstances, the balance between proliferation and programmed cell death, usually in the form of apoptosis, is maintained by tightly regulating both processes to ensure the integrity of organs and tissues. Mutations in DNA that lead to cancer (only certain mutations can lead to cancer and the majority of potential mutations will have no bearing) disrupt these orderly processes by disrupting the programming regulating the processes.

Carcinogenesis is caused by this mutation of the genetic material of normal cells, which upsets the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. The uncontrolled and often rapid proliferation of cells can lead to benign tumors; some types of these may turn into malignant tumors (cancer). Benign tumors do not spread to other parts of the body or invade other tissues, and they are rarely a threat to life unless they compress vital structures or are physiologically active, for instance, producing a hormone. Malignant tumors can invade other organs, spread to distant locations (metastasis) and become life-threatening.

More than one mutation is necessary for carcinogenesis. In fact, a series of several mutations to certain classes of genes is usually required before a normal cell will transform into a cancer cell. Only mutations in those certain types of genes that play vital roles in cell division, apoptosis (cell death), and DNA repair will cause a cell to lose control of its cell proliferation.

Oncovirinae, retroviruses that contain an oncogene, are categorized as oncogenic because they trigger the growth of tumorous tissues in the host. This process is also referred to as viral transformation.

Cancer is fundamentally a disease of regulation of tissue growth. In order for a normal cell to transform into a cancer cell, genes that regulate cell growth and differentiation must be altered. Genetic changes can occur at many levels, from gain or loss of entire chromosomes to a mutation affecting a single DNA nucleotide. There are two broad categories of genes that are affected by these changes. Oncogenes may be normal genes that are expressed at inappropriately high levels, or altered genes that have novel properties. In either case, expression of these genes promotes the malignant phenotype of cancer cells. Tumor suppressor genes are genes that inhibit cell division, survival, or other properties of cancer cells. Tumor suppressor genes are often disabled by cancer-promoting genetic changes. Typically, changes in many genes are required to transform a normal cell into a cancer cell.

There is a diverse classification scheme for the various genomic changes that may contribute to the generation of cancer cells. Most of these changes are mutations, or changes in the nucleotide sequence of genomic DNA. Aneuploidy, the presence of an abnormal number of chromosomes, is one genomic change that is not a mutation, and may involve either gain or loss of one or more chromosomes through errors in mitosis.

Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains many copies (often 20 or more) of a small chromosomal region, usually containing one or more oncogenes and adjacent genetic material. Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukemia, and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase.

Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter of a gene and affect its expression, or may occur in the gene's coding sequence and alter the function or stability of its protein product. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, and such an event may also result in the expression of viral oncogenes in the affected cell and its descendants.