Chromosome 2q24.2 is lost in sporadic but not in BRCA1-associated ovarian carcinomas.
Journal - Pathology (England )
AIMS: Comparison between BRCA1-associated and sporadic ovarian carcinomas is a potential method to identify candidate modifier gene/s involved in the carcinogenic pathway of either or both groups. A previous study identified a significant difference in the frequency of copy number gain at 2q24-q32 by comparing BRCA1-associated and sporadic ovarian tumour specimens using comparative genomic hybridisation (CGH). The present study aimed to investigate the reported allelic imbalance at 2q24-32 by amplification of several microsatellite markers at the region by quantitative microsatellite analysis (QuMA) using Taqman at the same region identified as a site of allelic imbalance. METHODS: The copy number of the genomic region in 2q24-32 was established in 21 BRCA1-associated ovarian carcinomas and 14 sporadic cases using quantitative microsatellite polymerase chain reaction (PCR). Statistical analysis was performed using permutation test analysis. RESULTS: A significant loss at D2S156 marker (2q24.2) (p = 0.026) compared with the other three markers at 2q24-32 was found in the sporadic cohort but not in the BRCA1-associated group (p = 0.385). CONCLUSIONS: Our data do not support the association between copy number gain at 2q24-32 and BRCA1 mutation status in ovarian cancers reported previously. The novel finding of the present study was significant loss at 2q24.2 in sporadic ovarian cancers.
|ISSN : ||0031-3025|
|Mesh Heading : ||Adenocarcinoma DNA, Neoplasm Female Gene Dosage Gene Expression Regulation, Neoplastic Humans Microsatellite Repeats Neoplasm Staging Ovarian Neoplasms Polymerase Chain Reaction metabolism pathology analysis metabolism pathology|
|Mesh Heading Relevant : ||Chromosome Deletion Chromosomes, Human, Pair 2 Genes, BRCA1 genetics genetics|
No differences in p53 mutation frequencies between BRCA1-associated and sporadic ovarian cancers.
Journal - Gynecologic oncology (United States )
OBJECTIVE: Mutation of the BRCA1 gene, which has incomplete penetrance, is involved in ovarian cancer development. Cell cycle check point inactivation via acquired somatic mutations in the check point regulatory genes, particularly p53, may be required for BRCA1-linked ovarian tumorigenesis. In the few studies directly comparing p53 mutations in BRCA1-linked and sporadic ovarian cancers, data have been contradictory. This study aimed to clarify the role of p53 mutation in BRCA1-associated and sporadic ovarian cancer by comparing two, large, matched cohorts from two different populations who developed BRCA1-linked or sporadic ovarian cancers. METHODS: Forty-eight BRCA1-associated ovarian tumor samples (22 from Australia and 26 from Norway) were collected and matched with 48 sporadic ovarian cancers for tumor stage, grade, histological subtype, and patient age. Expression of p53 protein was measured by immunohistochemistry (IHC). RESULTS: Consistent with the presence of a mutated p53 protein, the majority of BRCA1-associated (79%) and sporadic (73%) ovarian carcinomas from Australia and Norway overexpressed p53 protein. There was no significant difference between BRCA1-linked ovarian cancers and their sporadic counterparts with regard to p53 protein expression (P = 0.5). CONCLUSION: Our results suggest that p53 inactivation is associated with both BRCA1-associated and sporadic ovarian tumorigenesis, and that BRCA1-linked and sporadic ovarian cancers may develop through a similar carcinogenic pathway.
|ISSN : ||0090-8258|
|Mesh Heading : ||Adult Aged Cohort Studies Female Gene Expression Regulation, Neoplastic Gene Silencing Genes, p53 Humans Immunohistochemistry Middle Aged Ovarian Neoplasms Tumor Suppressor Protein p53 metabolism pathology biosynthesis genetics|
|Mesh Heading Relevant : ||Genes, BRCA1 Germ-Line Mutation Mutation, Missense genetics genetics|