The table in this problem summarizes some of the data that have been collected on mutations in the BRCA1 tumor-suppressor gene in families with a high incidence of both early-onset breast cancer and ovarian cancer.

Predisposing Mutations in BRCA1
Kindred    Codon    Nucleotide     Coding Effect     Frequency in
                               Change                                    Control
                                                                                Chromosomes    
 1901          24           -11 bp          Frameshift           0/180
                                                       or splice
 2082        1313         C→T           Gln→Stop            0/170
 1910        1756         Extra C        Frameshift           0/162
 2099        1775         T→G            Met→Arg            0/120
 2035         NA*          ?                  Loss of                NA*
                                                       transcript                                      _
Source: (1994). Science 266:66–71. © AAAS.

Examine the types of mutations that are listed in the table, and determine if the BRCA1 gene is likely to be a tumor-suppressor gene or an oncogene.

Key Concepts

Tumor-Suppressor Genes

Tumor-suppressor genes are crucial for regulating cell growth and preventing uncontrolled cell division. When these genes are mutated, their ability to control the cell cycle is compromised, leading to increased risk of cancer. The BRCA1 gene is a well-known tumor-suppressor gene, and mutations in it are associated with a higher incidence of breast and ovarian cancers.

Types of Mutations

Mutations can be classified into several types, including point mutations, insertions, deletions, and frameshifts. Point mutations involve a change in a single nucleotide, while insertions and deletions can alter the reading frame of the gene, potentially leading to a nonfunctional protein. Understanding these mutations is essential for assessing their impact on gene function and cancer risk.

Oncogenes vs. Tumor-Suppressor Genes

Oncogenes are mutated forms of normal genes (proto-oncogenes) that promote cell division and survival, often leading to cancer when overactive. In contrast, tumor-suppressor genes, like BRCA1, normally inhibit cell growth. The distinction between these two types of genes is vital for understanding cancer biology and the mechanisms by which mutations contribute to tumorigenesis.