Overview

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.

When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.

Such genes that act as the drivers for cancer are termed cancer-critical genes and are categorized into two broad classes - proto-oncogenes and tumor suppressor genes. In their normal state, proto-oncogenes encode for proteins involved in cell cycle regulation that control cellular growth and division. But gain-of-function mutations in proto-oncogenes turn them into overactive forms called oncogenes that make the cells grow out of control, leading to cancer. In most cases,  these cancer-causing mutations are acquired and not inherited. Some of the most common examples of proto-oncogenes in humans are Ras, HER2, Myc, and Cyclic D.

The major difference between proto-oncogenes and tumor suppressor genes is that proto-oncogenes lead to cancer upon over-activation, while tumor suppressor genes cause cancer when they are inactivated

Procedure

Cancer-critical genes are a group of genes that, upon mutation or alteration, contribute to the development of cancer. 

These genes can be categorized into two major classes based on how the mutation affects gene activity - proto-oncogenes and tumor-suppressor genes.

Under normal conditions, proto-oncogenes encode for proteins that act as signals for cell division. A gain-of-function mutation in the proto-oncogenes converts them into an overactive form called oncogenes.

The activation of oncogenes leads to overexpression of the cell-growth proteins resulting in uncontrolled cell proliferation and, hence, the formation of a tumor.

Gain-of-function mutations in proto-oncogenes are usually dominant, and even a single mutation can transform them into an oncogene.

For example, the proto-oncogene Ras encodes for an intracellular signal-transduction protein, Ras. Upon activation, Ras switches ON the cell growth signaling cascades. Upon mutation, the Ras gene turns into an oncogene and produces a mutated protein. This mutated Ras switches ON the signaling pathways, even in the absence of any activation signals, leading to the uncontrolled growth of cells and, ultimately, tumor formation.