Accession Number : AD1017955


Title :   The Fanconi Anemia BRCA Pathway as a Predictor of Benefit from Bevacizumab in a Large Phase-3 Clinical Trial in Ovarian Cancer


Descriptive Note : Technical Report,30 Sep 2013,29 Sep 2014


Corporate Author : University of Washington Seattle United States


Personal Author(s) : Swisher,Elizabeth M


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1017955.pdf


Report Date : 01 Oct 2014


Pagination or Media Count : 6


Abstract : We have completed DNA sequencing using BROCA-HR assay developed by our group for 65 DNA repair genes using blood DNA from two clinical trials in advanced ovarian cancer, GOG 218, N=773 and GOG 262, N=573. 278(14.7 ) had mutations in BRCA1 (182) and BRCA2 (96). 109 (5.8 ) had 112 mutations in the following genes: BRIP(27), CHEK2 (13), RAD51D (11), PALB2 (11), ATM (11), RAD51C (10), NBN (9), TP53 (6), BARD1 (4), MSH6 (4),FAM175A (3), PMS2 (2), and MLH1 (1). Consistent with their role as ovarian cancer susceptibility genes, BRIP1,RAD51C, and RAD51D were significantly more frequently mutated in OC than in the ESP (all P0.001). PALB2 andBARD1, which are not proven ovarian cancer genes, were also significantly more frequently mutated in OC (PALB2:OR of 11.0 , 95 CI [2.4 50], p=0.0003; BARD1: OR 31, 95 CI [1.7 577], p=0.02. ATM, NBN, CHEK2, andFAM175A mutations were not significantly more common in OC. Overall, we determined that at least 11 genes contribute to ovarian cancer and explain 20 of cases.


Descriptors :   ovarian cancer , neoplasms , therapeutics , dna sequence analysis , drug therapy , carcinoma , patient care , chemotherapy , oncology clinical trials , histology , MUTATIONS


Distribution Statement : APPROVED FOR PUBLIC RELEASE