Two somatic mutations in this gene have recently selleck kinase inhibitor been found in ovarian cancer. Our results suggest that in the primary tumor, BRCA1 mutations might, in combination with TP53, NF1 and TARBP1 mutations contribute to the metastasis and relapse after chemotherapy. Analyzing the interaction between the RAS, BRCA1 and TP53 mediated pathways in ovarian cancer could be therapeutically worthwhile, Inhibitors,Modulators,Libraries especially if considered in combination. We also show that valuable additional information re garding structural rearrangements can be derived from exome data. The CNV landscapes in our samples are asso ciated with known ovarian cancer mutations. Interesting examples include the amplification of 8q, which is likely driven by the MYC oncogene, and the amp lification of 11q13, which is common in breast and ovar ian carcinoma.

In addition, we observed deletion of chromosome 4, which has been shown to house several tumor suppressor genes, and deletions in chromosome 4 are associated with BRCA related tumours. These mutations Inhibitors,Modulators,Libraries are likely acting combinatorially to drive the de velopment of ovarian cancer. It is interesting to note Inhibitors,Modulators,Libraries that all of these genomic rearrangements Inhibitors,Modulators,Libraries are already present in the primary tumor, suggesting that large scale mutations accumulate quickly in early oncogenesis of ovarian cancer. Conclusions This work used whole exome capture and massively parallel DNA sequencing to study targeted candidate mutations in selected genes, as well as performing a hypothesis free analysis where we aimed to identify po tential driver mutations by identifying variants with in creased proportion of mutant alleles.

Genetic evolution of tumors from diagnosis to relapse after chemotherapy was not observed. Instead, we suggest that most of the critical tumor driving and chemotherapy resistant muta tions were already present in the primary tumor. We show that high throughput sequencing is effective in detecting large chromosomal rearrangements such as deletions and amplifications Inhibitors,Modulators,Libraries that occur in cancer. It is notable that the patient responded very poorly to platinum based therapy. relapse after only 3 course of therapy usually betokens a very poor survival. This early platinum failure is somewhat less common in BRCA1 related cancer than in non hereditary ovarian cancer, and it seems unlikely that this failure is related to type of mutation that was present in this patient.

The large number of deleterious somatic mutations present in the primary tumor likely contributed to the rapid progression of the disease. It will be important to conduct studies such as ours in large numbers of patients to establish whether spe cific exomic profiles at initial diagnosis are associated with subsequent resistance to standard neither chemotherapy. In these situations, alternative forms of first line therapy may be chosen.