The HER2 gene, also known as ERBB2, provides instructions for making a protein found on the surface of cells. This protein acts like a receiver, picking up signals that tell cells when to grow and divide. In healthy cells, HER2 plays a role in repairing cells and creating new ones, contributing to normal cell development and function.
When the HER2 gene functions as intended, it helps regulate the precise timing and rate of cell growth. However, alterations to this gene can disrupt this delicate balance. Such changes can lead to the HER2 protein signaling cells to grow and divide uncontrollably.
Understanding HER2 and Gene Mutations
The HER2 protein, or Human Epidermal Growth Factor Receptor 2, is found on the outer membrane of cells. It receives external signals that prompt cell growth, division, and repair. HER2 activates by partnering with other proteins in its family or with other HER2 proteins when abundant on the cell surface.
A gene mutation is a change in the normal DNA sequence of a gene. This alteration modifies the instructions for building a specific protein, leading to one that is overactive or does not function correctly. For HER2, a gene mutation can cause an abnormal increase in HER2 proteins on the cell surface. This overabundance leads to constant growth signals, causing uncontrolled cell proliferation and contributing to tumor development.
Acquired vs. Inherited HER2 Mutations
HER2 gene mutations are categorized into two types: acquired (somatic) and inherited (germline). Most HER2 gene mutations are acquired, developing during a person’s lifetime rather than being passed down from parents.
Acquired mutations are present only in certain cells or tissues, such as tumor cells, and are not present at birth. In contrast, inherited mutations are present in every cell of the body, passed down from a parent. Inherited HER2 gene mutations are rare and are not the usual cause of conditions associated with HER2 gene alterations. Therefore, having a close relative with HER2-positive cancer does not increase an individual’s risk for the same condition.
Factors Contributing to Acquired HER2 Mutations
Acquired HER2 gene mutations primarily result from random errors during DNA replication and cell division. These errors are a natural part of cellular processes, occurring constantly as cells reproduce. The body possesses complex DNA repair mechanisms designed to correct most of these errors. However, sometimes an error persists, leading to a permanent change in the gene’s DNA sequence.
With increasing age, the accumulation of these random errors becomes more likely. Additionally, the efficiency of the body’s DNA repair mechanisms can sometimes decrease with age, increasing the chance of acquired mutations, including those in the HER2 gene. This explains why the risk of many cancers, which are driven by such mutations, generally increases with age.
While general exposure to environmental carcinogens, such as those from smoking or radiation, can cause DNA damage and mutations in various genes, there is no strong, direct, or well-defined link between specific environmental exposures and the direct causation of HER2 gene mutations. For HER2, random errors during cell division are considered the predominant factor in the development of acquired mutations. Unlike some other health conditions where specific lifestyle choices or dietary habits are known to directly contribute to or prevent certain genetic changes, there are currently no known specific behaviors or environmental factors that directly cause or can prevent HER2 gene mutations from occurring.