Multi-omics analysis in suspected hereditary breast and ovarian cancer cases reveals novel candidate susceptibility factors
Related Experiment Video
Updated: Jul 2, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
B Aldrige Allister1, Winfried Hofmann1, Jonathan L Lühmann1
1Department of Human Genetics, Hannover Medical School, Hannover, Germany.
Abstract:
More than 80% of patients who meet clinical criteria for hereditary breast and ovarian cancer (HBOC) do not show pathogenic variants in BRCA1, BRCA2, and other diagnostically consented core genes. We hypothesized that variants in further DNA repair genes, cryptic genomic alterations, or polygenic factors may explain HBOC risk. We studied 134 patients with breast cancer and/or ovarian cancer by the use of whole genome sequencing (WGS), whole transcriptome sequencing (WTS), optical genome mapping (OGM), and mobile element analysis. We identified (likely) pathogenic variants in DNA repair genes in 18 patients, including several RECQ helicase and other DNA repair genes, an intragenic FANCM deletion, and six rare mobile element insertions (MEIs) in DNA repair genes. Incorporating PRS306 shifted estimated lifetime breast cancer risk by ≥5 percentage points in a subset of women (n = 75), including carriers of rare variants in DNA repair genes, resulting in both upward and downward risk estimation.
Related Concept Videos
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Cancers Originate from Somatic Mutations in a Single Cell
Cancers Originate from Somatic Mutations in a Single Cell
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
