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

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 P<0.001). 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.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2014
Accession Number
AD1017955

Entities

People

  • Elizabeth M Swisher

Organizations

  • University of Washington

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Biomedical Research
  • Blood
  • Cancer
  • Clinical Trials
  • Department Of Defense
  • Dna Sequence Analysis
  • Drug Therapy
  • Electronic Mail
  • Genetic Techniques
  • Genetic Testing
  • Hematologic Diseases
  • Histology
  • Mutations
  • Neoplasms
  • Ovarian Cancer
  • Survival

Fields of Study

  • Biology

Readers

  • Aerospace Engineering
  • Molecular and genetic basis of cancer.
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology