Characteristics of Colorectal Cancer (CRC) Patients with BRCA1 and BRCA2 Mutations


Madiha Naseem, Joanne Xiu, Mohamed Salem, Richard M. Goldberg, Ari Vanderwalde, Axel Grothey, Philip Agop Philip, Andreas Seeber, Alberto Puccini,Ryuma Tokunaga, Francesca Battaglin, Martin D. Berger, Afsaneh Barzi, Diana Hanna, Wu Zhang, Jimmy J. Hwang, Anthony Frank Shields, John Marshall, Wolfgang Michael Korn, Heinz-Josef Lenz


  • BRCA1 and BRCA2 are important tumor suppressor proteins involved in double-stranded DNA break repair using homologous recombination.1
  • In 1994, the Breast Cancer Linkage Consortium presented an increased risk of colorectal cancer (CRC) among BRCA1 mutation carriers, which ushered more research into BRCA1 genetic alterations in CRC.1
  • To date, studies have shown that BRCA1/2 mutations increase the risk of CRC and are associated with earlyonset disease, younger age, MSI and left-sided tumors. 2,3 However, further characterization of these mutations in CRC is needed to better understand their prognostic role.


  • A total of 6396 CRC tumor samples were tested with NextGeneration Sequencing (NGS) on a 592-gene panel
  • Pathogenic or presumed pathogenic variants were counted as mutations (mt).
  • Microsatellite instability (MSI) and tumor mutational burden (TMB) were tested by NGS.
  • Statistical correlations were investigated using ANOVA, Chisquare and t-test.


  • This is the first study to show that BRCA1/2 mutations are more frequent in MSI-H, independently associated with higher TMB, pathogenic POLE
    mutations, and right-sided tumors in CRCs.
  • Given their relationship with TMB in MSS tumors, the presence of BRCA1/2 mutations are indicator for impaired DNA damage repair and could be potential
    predictive biomarkers for checkpoint or PARP inhibitors in CRC, a finding that should be prospectively evaluated.

Download Publication