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ASCOBT 2023: Interplay of DNA Damage Response Variants and the Transcriptome in East Asian Patients With Prostate Cancer

By: Julia Fiederlein Cipriano, MS
Posted: Monday, August 21, 2023

Melvin Lee Kiang Chua, MBBS, FRCR, PhD, FAMS, of the National Cancer Centre Singapore, and colleagues previously reported that the prevalence of germline DNA damage response mutations in East Asian patients with localized prostate cancer was comparable to that of their White counterparts. Building upon this work, during the 2023 American Society of Clinical Oncology (ASCO) Breakthrough meeting (Abstract 75) in Yokohama, Japan, they presented their findings regarding the intricate interplay between these variants and the somatic tumor transcriptome.

The investigators focused on 172 East Asian patients who underwent central assessment for Gleason score. Approximately 15.0% of this population appeared to harbor DNA damage response variants; this rate was found to be similar to that of an 890-patient cohort from the same institution. Among the DNA damage response mutations, 7.7% and 92.3% were classified as pathogenic or likely pathogenic and conflict-of-interest pathogenic, respectively.

Tumor transcriptome profiling scores seemed to be comparable between patients with and without DNA damage response mutations (median, 0.87 vs. 0.53; P = .10). The investigators did not observe a difference for the basal (P = .48) and luminal (P = .21) prostate cancer subtypes. Patients with and without DNA damage response mutations appeared to demonstrate comparable expression of DNA repair gene sets (median score, –0.2 vs. –0.17). However, the investigators reported microenvironment differences for immune-related genes; patients with DNA damage response mutations were found to exhibit a less immunosuppressive environment than those without (PD-L2: –0.15 vs. 0.2; regulatory T cells: 0.09 vs. 0.13; myeloid-derived suppressor cells: 0.03 vs. 0.07).

“Our findings suggest the influence of germline DNA damage response variants that extends beyond tumorigenesis,” the investigators concluded.

Disclosure: For full disclosures of the study authors, visit

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