Why do mutations in genes such as BRCA1, BRCA2, and PALB2 increase cancer risk in an autosomal dominant inheritance pattern?

Question

Why do mutations in genes such as BRCA1, BRCA2, and PALB2 increase cancer risk in an autosomal dominant inheritance pattern?

BlackTom AI · Accepted Answer

Question: Why do mutations in genes such as BRCA1, BRCA2, and PALB2 increase cancer risk in an autosomal dominant inheritance pattern?

Option a: The mutated gene directly causes cancer in cells without needing any additional genetic changes. While these genes are linked to cancer risk, the classic explanation for autosomal dominant risk with these tumor suppressor genes is not that a single mutated gene directly causes cancer by itself. Instead, cancer typically arises when a second, normal copy is lost or inactivated in a cell, so this option oversimplifies the mechanism and ignores the two-hit hypothesis.

Option b: A person inherits one mutated copy, meaning that if the second copy becomes damaged later, no functional tumor suppressor remains. This aligns with the classic two-hit model for tumor suppressor genes: one inherited mutated allele predisposes to cancer, and a somatic event inactivates the remaining healthy allele, leading to loss of tumor-suppressor function in a cell and potential tumor development. This explains the autosomal dominant inheritance pattern in a familial context while requiring a second hit for cancer to arise.

Option c: The mutated genes produce proteins that actively cause cells to divide uncontrollably. BRCA1/BRCA2/PALB2 are tumor suppressor genes, whose normal function is to help prevent uncontrolled growth. When mutated, they typically lose function rather than gaining function that actively drives division. This option describes an oncogene-like behavior rather than the loss-of-function mechanism typical of BRCA-related cancer risk, making it inaccurate.

Option d: Only one mutated copy is enough to eliminate all tumor-suppressor function permanently. In most cases involving BRCA1/BRCA2/PALB2, losing one functional copy does not completely eliminate tumor-suppressor activity across all cells; cancer risk increases because a second allele can be lost in a particular cell, not because a single germline mutation eliminates function everywhere. This overstates the effect of a single mutated copy and ignores the necessity of a second somatic event in the same cell.

In summary, option b correctly captures the autosomal dominant pattern by noting that inheriting one mutated copy predisposes to cancer, and a subsequent somatic event inactivates the second copy, removing tumor-suppressor activity in a cell. The other options misstate the role of tumor suppressor genes, the necessity of a second hit, or the mechanism by which these mutations contribute to cancer risk.

Why do mutations in genes such as BRCA1, BRCA2, and PALB2 increase cancer risk in an autosomal dominant inheritance pattern?

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