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.
Although the mutations listed in the table are clearly deleterious and cause breast cancer in women at very young ages, each of the kindred groups had at least one woman who carried the mutation but lived until age 80 without developing cancer. Name at least two different mechanisms (or variables) that could underlie variation in the expression of a mutant phenotype, and propose an explanation for the incomplete penetrance of this mutation. How do these mechanisms or variables relate to this explanation?
19. Cancer Genetics
Cancer Mutations