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ERBB2, often called HER2, is a gene that provides the code for making a cell surface protein called the ErbB2 (HER2) growth factor receptor. When certain growth factors (proteins that stimulate cell growth and division) bind to this receptor, they activate a signaling system inside the cell that ultimately promotes diverse functions such as growth, interaction and adhesion between cells, and ability of the cell to migrate within tissues. In some tumors, the activation of HER2 signaling is an important mechanism that drives the disease process. This can occur through HER2 gene amplification (the most common mechanism) or HER2 gene mutation in the cancer cells.
Extra copies of the HER2 gene (gene amplification) have been found in a number of different cancers. This causes the cancer cells to make excess HER2 (overexpression), which in turn, tells the cells to grow and divide in an uncontrolled manner. The presence of amplified HER2 has been reported in approximately 25% of breast tumors, 20% of esophageal tumors, 15% of gastric cancers and 20% of certain ovarian tumors. The FDA has approved the targeted therapies including trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb), and T-DM1 (Kadcyla) for the treatment of patients with certain kinds of breast cancer in which HER2 is overexpressed. Trastuzumab is also FDA approved to treat gastric cancer with amplification of this receptor.
Mutations in HER2 involving small duplications of the gene can promote resistance to some EGFR targeted therapies, but on the other hand, promote response to certain HER2 inhibitors. While very rare, these mutations are most often associated with non-small cell lung cancer, but have also been described in other malignancies including brain, gastric, breast and ovarian tumors. Tumor mutation profiling performed clinically at the MGH Cancer Center has identified HER2 mutations in a small subset of non-HER2 amplified breast cancer (1%) and non-small cell lung cancers (1%).
Source: Genetics Home Reference
The ERBB2 gene encodes for a cell surface protein that belongs to the ERBB family of receptor tyrosine kinases, known as ErbB2 (more commonly referred to as HER2). Four members of the ERBB family have been identified; EGFR (ERBB1, HER1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). Binding of a ligand induces ERBB receptor homo-/hetero-dimerization and triggers a signaling cascade that drives many cellular responses. These include the activation of PI3K/AKT/mTOR and MAP kinase/ERK pathways, which promote cell survival and proliferation. Although there is no known ligand for HER2, HER2 is the preferred dimerization partner for the other ERBB receptors. In some cancers, HER2 activity is increased through protein overexpression or gene mutation.
The overexpression of HER2 is tightly associated with amplification of the HER2 gene. HER2 amplification has been reported in multiple malignancies, including breast cancer (25% incidence), esophageal cancer (20% incidence), gastric cancer (15% incidence), and mucinous ovarian carcinomas (20% incidence).
Mutations in HER2 have also been identified as an important mechanism that could drive tumor growth and confer resistance to targeted therapies. In-frame duplication/insertions in a region of HER2 exon 20 that is conserved with EGFR have been demonstrated in ~2% of lung cancer patients. Mutations in HER2 receptor have also been described in a small subset of non-HER2 amplified breast cancer (1%).
Source: Genetics Home Reference
The mutation of a gene provides clinicians with a very detailed look at your cancer. Knowing this information could change the course of your care. To learn how you can find out more about genetic testing please visit http://www.massgeneral.org/cancer/news/faq.aspx
or contact the Cancer Center.