American Association for Cancer Research
10780432ccr205037-sup-258099_2_supp_7048045_qrgqz8.pdf (8 MB)

Supplementary Methods from Detection of Molecular Signatures of Homologous Recombination Deficiency in Bladder Cancer

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journal contribution
posted on 2023-03-31, 22:42 authored by Judit Börcsök, Miklos Diossy, Zsofia Sztupinszki, Aurel Prosz, Viktoria Tisza, Sandor Spisak, Orsolya Rusz, Dag R. Stormoen, Helle Pappot, Istvan Csabai, Søren Brunak, Kent W. Mouw, Zoltan Szallasi

Description of supplementary materials and methods.


Research and Technology Innovation Fund

Breast Cancer Research Foundation

Kræftens Bekæmpelse

Novo Nordisk Foundation

Prostate Cancer Research Program

Det Frie Forskningsråd Sundhed og Sygdom


Velux Foundation



Poly (ADP ribose)-polymerase (PARP) inhibitors are approved for use in breast, ovarian, prostate, and pancreatic cancers, which are the solid tumor types that most frequently have alterations in key homologous recombination (HR) genes, such as BRCA1/2. However, the frequency of HR deficiency (HRD) in other solid tumor types, including bladder cancer, is less well characterized. Specific DNA aberration profiles (mutational signatures) are induced by HRD, and the presence of these “genomic scars” can be used to assess the presence or absence of HRD in a given tumor biopsy even in the absence of an observed alteration of an HR gene. Using whole-exome and whole-genome data, we measured various HRD-associated mutational signatures in bladder cancer. We found that a subset of bladder tumors have evidence of HRD. In addition to a small number of tumors with biallelic BRCA1/2 events, approximately 10% of bladder tumors had significant evidence of HRD-associated mutational signatures. Increased levels of HRD signatures were associated with promoter methylation of RBBP8, which encodes CtIP, a key protein involved in HR. A subset of bladder tumors have genomic features suggestive of HRD and therefore may be more likely to benefit from therapies such as platinum agents and PARP inhibitors that target tumor HRD.

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