Table 3.

Comparison of p53 mutations found in BRCA1-related and sporadic breast tumors

A. Comparison of p53 mutations found in BRCA1-related and sporadic breast tumors
BRCA1 (n = 21)Sporadic (n = 37)BRCA1 vs sporadic
%n%nP *
Total mutations5167
Mutation type
    Deleterious missense
        Hotspot (common hotspot) 21.6% (17.6%)11 (9)25.4% (20.9%)17 (14)
        Non-hotspot11.8%614.9%10
        Nonsense9.8%51.5%1
        Splice2.0%10.0%0
    Neutral
        Missense-neutral21.6%1132.8%22
        Silent19.6%1020.9%14
    Deleterious insertions/deletions
        Frameshift (leading to truncation)9.8%51.5%1
        In-frame insertion/deletion3.9%23.0%2
    Mutation effect
        Deleterious missense/in-frame37.3%1943.3%291.0000
        Truncating mutations 21.6%113.0%20.0061
        Neutral mutations41.2%2153.7%360.5908
B. Logistic regression analysis
Truncating mutations §Common hotspot
ORPORP
p53IHC+ status (controlled for BRCA1 status )0.0369 **0.006725.20.0001
BRCA1 status (controlled for p53IHC status)24.50.00120.91870.9067
  • NOTE: A. For this comparative analysis, only mutations with an abundance of ≥25% were used. B. Logistic regression analysis: prediction of the influence of p53IHC status and BRCA1 status on the presence of p53 truncation or hotspot mutations in the tumor DNA. Independent multivariate analysis 1: prediction of the influence of p53IHC status on the outcome of truncating mutations or hotspot mutations, controlling for the influence of BRCA1 status. Independent multivariate analysis 2: vice versa: prediction of the influence of BRCA1 status on the outcome of truncating mutations or hotspot mutations, controlling for the influence of p53IHC status.

  • * P values were calculated using Bonferroni-corrected Fisher's exact test, and P values of <0.01 are printed in bold print.

  • Mutations that occur at p53 hotspot codons were predicted deleterious by the SIFT algorithm.

  • Truncating mutations are frameshift, splice, and nonsense mutations.

  • § Truncating mutations are frameshift, splice, and nonsense mutations.

  • Common hotspot mutations occur significantly more often (P < 0.001) than other mutations (see Materials and Methods).

  • p53IHC status of tumors in the sporadic tumor group matched that of the BRCA1 tumor group.

  • ** p53IHC+ tumors have an OR of 0.0369 to have a truncating mutation; therefore, p53IHC− tumors have an OR of 27.1 (=1/0.0369) to have a truncating mutation.