Germline Mutation

A germline mutation is a gene change inherited from a parent, or present from conception, that is found in every cell of the body. It differs from a somatic mutation, which arises later only in the tumor. Some germline mutations, such as in the BAP1 gene, raise a person's risk of mesothelioma and other cancers.

Origin

The terms germline and somatic come from biology's distinction between reproductive (germ) cells and the rest of the body. Inherited cancer syndromes were mapped to specific genes from the 1990s onward, and germline BAP1 mutations were linked to mesothelioma in families in 2011.

Significance in Asbestos Context

Most gene changes found when a mesothelioma is tested are somatic, acquired in the tumor; only a blood or saliva test can show whether a mutation is germline. Studies suggest a small minority of mesothelioma patients, often estimated at a few percent, carry a germline mutation in BAP1 or another cancer-risk gene. Carriers tend to be diagnosed younger, are more often women or have peritoneal disease, and may live longer. Defendants sometimes argue that a germline mutation, not asbestos, caused the cancer. The mainstream view is that these mutations raise susceptibility, and that asbestos exposure and inherited risk can act together; many carriers with mesothelioma had asbestos exposure. Germline results also matter to relatives, who may want testing and screening. Many specialists now recommend offering germline testing to mesothelioma patients, usually with genetic counseling.

Example Sentence

Her tumor showed loss of BAP1, and a blood test then found a germline BAP1 mutation, so her children were referred for genetic counseling.

Related Terms

Somatic Mutation, BAP1, BAP1 Tumor Predisposition Syndrome, Tumor Suppressor Gene, Genetic Counseling, Idiopathic Mesothelioma, Specific Causation

Notes

• Ask whether a test result is from the tumor (somatic) or from blood or saliva (germline); they mean different things.
• Genetic counseling before and after testing helps you and your family understand the results.
• Tell your lawyer if you have had, or are considering, genetic testing, since results may be requested in a case.
• A family history of mesothelioma, melanoma of the eye or kidney cancer is worth mentioning to your doctor.