Recurrent copy number alterations in BRCA1-mutated ovarian tumors alter biological pathways.
Array CGH was used to identify recurrent copy number alterations (RCNA) characteristic of either BRCA1-related or sporadic ovarian cancer. After preprocessing, both groups of patients were modeled using a recurrent Hidden Markov Model to detect RCNA. RCNA with a probability higher than 80% were called. After removing RCNA present in both groups, the genes present in the remaining RCNA were investigated for enrichment of pathways from external databases. More RCNA were observed in the BRCA1 group, and they display more losses than gains compared to the sporadic group. When focusing on the type of RCNA, no significant difference in length was seen for the gains, but there was a statistically significant difference for the losses. In the sporadic group, a great proportion of the altered regions contain genes known to have a function in cell adhesion and complement activation, whereas the BRCA1 samples are characterized by alterations in the HOX genes, metalloproteinases, tumor suppressor genes, and the estrogen-signaling pathways. We conclude that BRCA1 ovarian tumors present a different type, number, and length of RCNA; a huge amount of the genome is lost, resulting in important genomic instability. Moreover, important biological pathways are altered differentially when compared to the sporadic group.
Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Katholieke Universiteit Leuven, Belgium. karin.leunen@uz.kuleuven.ac.be
Karin
K
Leunen
Olivier
O
Gevaert
Anneleen
A
Daemen
Vanessa
V
Vanspauwen
Geneviève
G
Michils
Bart
B
De Moor
Philippe
P
Moerman
Ignace
I
Vergote
Eric
E
Legius
D019313:BRCA1 Protein / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D008390:Markov Chains; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
D019313:BRCA1 Protein