Tumor Suppressor Genes: Retinoblastoma

Proto-oncogenes

Genes that, when mutated, lead to overactive or overexpressed proteins contributing to cancer.

Tumor Suppressor Genes

Genes that, when mutated, result in a loss-of-function, leading to uncontrolled cell growth.

Knudson's Two-Hit Hypothesis

Theory that two genetic hits (mutations) are required to inactivate both copies of a tumor suppressor gene to promote tumor formation.

Retinoblastoma

A childhood eye tumor caused by mutations in the Rb gene, serving as a classic model for tumor suppressor gene inactivation.

Loss of Heterozygosity (LOH)

A process where a cell loses one allele of a gene, often leading to the inactivation of tumor suppressor genes.

Mitotic Recombination

A mechanism that can lead to loss of a wild-type copy of a gene, resulting in LOH.

Promoter Methylation

An epigenetic modification that silences gene expression by adding methyl groups to the promoter region.

Rb (Retinoblastoma protein)

A tumor suppressor protein that regulates the cell cycle by preventing entry into the S-phase.

E2F transcription factors

Proteins that promote the transcription of genes required for S-phase entry, regulated by Rb.

Cyclin D-CDK4/6 and CycE-CDK2

Protein complexes that phosphorylate Rb, leading to its inactivation and allowing cell cycle progression.

HPV E7

An oncoprotein from Human Papillomavirus that binds Rb, inactivating it and promoting uncontrolled cell cycle progression.

Familial Retinoblastoma

A form of retinoblastoma characterized by multiple tumors and a genetic predisposition.

Sporadic Retinoblastoma

A form of retinoblastoma usually presenting as a single tumor and requiring independent mutations.

Cancer-Critical Genes

Genes that play a crucial role in cancer development, categorized into proto-oncogenes and tumor suppressor genes.

Epigenetic modification

Changes in gene expression without altering the DNA sequence, often through mechanisms such as promoter methylation.