Increased frequency of TP53 mutations in BRCA1 and BRCA2 ovarian tumours.
We screened 81 ovarian tumours (30 BRCA1 associated, 18 BRCA2 associated, and 33 sporadic) for somatic TP53 mutations using both DNA analysis and immunostaining. TP53 mutations were significantly more frequent in tumours with mutations in BRCA1 (70% by immunostaining and 60% by DNA analysis) and BRCA2 (67% and 50%) compared to sporadic controls (39% and 30%) (P = 0.009). A higher proportion of tumours with BRCA1 and BRCA2 mutations were poorly differentiated, and TP53 mutant tumours in all categories were also more likely to be poorly differentiated. The poor differentiation of tumours with BRCA1 and BRCA2 mutations may be directly related to the role of these genes in DNA repair, and the need to overcome cell cycle checkpoints, often through loss of TP53. These results are consistent with the model of BRCA-induced tumorigenesis in which loss of checkpoint control is necessary for tumour development.
Ramus
S J
SJ
CRC Human Cancer Genetics Research Group, Strangeways Research Laboratory, Cambridge, UK.
Bobrow
L G
LG
Pharoah
P D
PD
Finnigan
D S
DS
Fishman
A
A
Altaras
M
M
Harrington
P A
PA
Gayther
S A
SA
Ponder
B A
BA
Friedman
L S
LS
D000483:Alleles; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53