What is the significance of mosaicism in hereditary cancer genetics?

• A. All cells carry the variant.
• B. Not all cells carry the variant; it can reduce detectability in blood tests and may require testing multiple tissues or deep sequencing.
• C. It guarantees detection on standard tests.
• D. It has no impact on testing.

Answer: (B)

Mosaicism means the disease-causing variant is present in only a subset of the body's cells, not all of them. In hereditary cancer genetics, this matters because if the variant isn’t in the cells being tested—often blood cells used for germline testing—it can be missed. The variant allele fraction may be low, so standard tests might not detect it, making deep sequencing or testing of multiple tissues (such as saliva, skin, or tumor tissue) necessary to uncover mosaic variants. This has important implications for risk assessment: mosaicism can explain cancer risk in the person even when blood tests are negative, and if the mosaic involve germ cells, there’s a potential for inheritance by offspring despite negative germline testing in blood.