PMID- 10070948
OWN - NLM
STAT- MEDLINE
DCOM- 19990317
LR  - 20190513
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 91
IP  - 5
DP  - 1999 Mar 3
TI  - Frequency of p53 mutations in breast carcinomas from Ashkenazi Jewish carriers of
      BRCA1 mutations.
PG  - 469-73
AB  - BACKGROUND: Breast carcinomas occurring in carriers of BRCA1 gene mutations may
      have a distinctly different pathway of molecular pathogenesis from those
      occurring in noncarriers. Data from murine models implicate loss of p53 (also
      known as TP53) gene function as a critical early event in the malignant
      transformation of cells with a BRCA1 mutation. Therefore, breast tumors from
      BRCA1 mutation carriers might be expected to exhibit a high frequency of p53
      mutations. This study examined the frequency of p53 mutations in the breast
      tumors of Ashkenazi Jewish carriers and noncarriers of BRCA1 mutations. METHODS: 
      Tumor DNA from carriers and noncarriers of BRCA1 mutations was screened for
      mutations in exons 4 through 10 of the p53 gene by use of the polymerase chain
      reaction and single-strand conformation polymorphism (SSCP) analysis of the
      amplified DNA. Direct sequencing was performed on gene fragments that showed
      altered mobility in SSCP analysis. RESULTS: Mutations in the p53 gene were
      detected in 10 of 13 tumors from BRCA1 mutation carriers versus 10 of 33 tumors
      from non-carriers (two-sided P = .007). The p53 mutations were distributed
      throughout exons 4 through 10 and included both protein-truncating and missense
      mutations in both groups. CONCLUSIONS: A statistically significantly higher
      frequency of p53 mutations was found in breast tumors from carriers of BRCA1
      mutations than from noncarriers, which adds to the accumulating evidence that
      loss of p53 function is an important step in the molecular pathogenesis of BRCA1 
      mutation-associated breast tumors. This finding may have implications for
      understanding phenotypic differences and potential prognostic differences between
      BRCA1 mutation-associated hereditary breast cancers and sporadic cancers.
FAU - Phillips, K A
AU  - Phillips KA
AD  - Center for Cancer Genetics and Samuel Lunenfeld Research Institute of Mt. Sinai
      Hospital, Toronto, ON, Canada.
FAU - Nichol, K
AU  - Nichol K
FAU - Ozcelik, H
AU  - Ozcelik H
FAU - Knight, J
AU  - Knight J
FAU - Done, S J
AU  - Done SJ
FAU - Goodwin, P J
AU  - Goodwin PJ
FAU - Andrulis, I L
AU  - Andrulis IL
LA  - eng
GR  - U01CA69467/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
CIN - J Natl Cancer Inst. 2001 Jan 17;93(2):151-2. PMID: 11208887
MH  - Adult
MH  - Breast Neoplasms/*ethnology/*genetics
MH  - DNA, Neoplasm/genetics
MH  - Female
MH  - Genes, BRCA1/*genetics
MH  - Genes, p53/*genetics
MH  - *Heterozygote
MH  - Humans
MH  - Jews/*genetics
MH  - Middle Aged
MH  - *Mutation
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Tumor Suppressor Protein p53/*genetics
EDAT- 1999/03/10 00:00
MHDA- 1999/03/10 00:01
CRDT- 1999/03/10 00:00
PHST- 1999/03/10 00:00 [pubmed]
PHST- 1999/03/10 00:01 [medline]
PHST- 1999/03/10 00:00 [entrez]
AID - 10.1093/jnci/91.5.469 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 1999 Mar 3;91(5):469-73. doi: 10.1093/jnci/91.5.469.