Optical Genome Mapping Identifies Clinically Relevant Genomic Rearrangements in Prostate Cancer Biopsy Sample

As recent clinical trials have shown, PARP inhibitor (PARPi) and androgen receptor signaling inhibitor (ARSi) abiraterone combination are most effective in BRCA1/2 mutated prostate cancer. The conflicting point is that PARPi and ARSi combination may or may not work in BRCA1/2 wild-type prostate cancer. There was notion that PARPi and ARSi treatment have synergistic effects, but clinical trial data does not fully support such an effect exists. Another possibility is that we may have missed BRCA1/2 genetic alteration in those patients.

Current standard methods of tumor genetic mutation evaluation are next generation sequencing and microarray(of tumor tissue and/or circulating tumor DNA), which is highly sensitive in detecting point mutation or copy number alteration. However, by using the optical genome mapping tool we found an inter-chromosomal translocation splitting the BRCA2 gene, which has been missed by DNA panel sequencing. The primary limitation of this study is its small size. We are currently running a larger project combining optical genome mapping and RNA sequencing to have a genome-wide view of structural variation affecting gene expression.

Prostate cancer has been recognized as a tumor of low mutational burden, and maybe it was because of the tools we used to gauze their genetic alterations. Long read sequencing tools and optical genome mapping may provide further cues on prostate cancer genomics.

Written by: Hyunho Han, Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea

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