Tumor suppressor gene

The loss of function for these genes may be even more significant in the development of human cancers, compared to the activation of oncogenes.

[4] The classification schemes are evolving as medical advances are being made from fields including molecular biology, genetics, and epigenetics.

The discovery of oncogenes and their ability to deregulate cellular processes related to cell proliferation and development appeared first in the literature as opposed to the idea of tumor suppressor genes.

[5] Alfred Knudson, a pediatrician and cancer geneticist, proposed that in order to develop retinoblastoma, two allelic mutations are required to lose functional copies of both the Rb genes to lead to tumorigenicity.

[5] This unique development pattern allowed Knudson and several other scientific groups in 1971 to correctly hypothesize that the early development of retinoblastoma was caused by inheritance of one loss of function mutation to an RB germ-line gene followed by a later de novo mutation on its functional Rb gene allele.

Unlike oncogenes, tumor suppressor genes generally follow the two-hit hypothesis, which states both alleles that code for a particular protein must be affected before an effect is manifested.

Knudson observed that the age of onset of retinoblastoma followed 2nd order kinetics, implying that two independent genetic events were necessary.

[9] Other tumor-suppressor genes that do not follow the two-hit rule are those that exhibit haploinsufficiency, including PTCH in medulloblastoma and NF1 in neurofibroma.

In most cases, tumor suppressor proteins inhibit the same cell regulatory pathways that are stimulated by the products of oncogenes.

The addition of a methyl group to either histone tails or directly on DNA causes the nucleosome to pack tightly together restricting the transcription of any genes in this region.

Stephen Baylin observed that if promoter regions experience a phenomenon known as hypermethylation, it could result in later transcriptional errors, tumor suppressor gene silencing, protein misfolding, and eventually cancer growth.

The two main approaches used currently to introduce genetic material into cells are viral and non-viral delivery methods.

[25][27] Before the vectors are inserted into the tumors of the host, they are prepared by having the parts of their genome that control replication either mutated or deleted.

[25] Non-viral gene therapy uses either chemical or physical methods to introduce genetic material to the desired cells.

[25][27] The liposome-coated plasmid method has recently also been of interest since they produce relatively low host immune response and are efficient with cellular targeting.

This allows for the discovery of novel tumor suppressors and can give insight on how to treat and cure different cancers in the future.