Targeted Germline Sequencing Identifies Ultra-Rare DDR Variants in High-Risk Prostate Cancer : Short title: Germline DDR Variants in High-Risk Prostate Cancer.
- 1Department of Biology, College of Science, Salahaddin University-Erbil, Kirkuk Road, 44001 Erbil, Kurdistan Region, Iraq.
Abstract
Prostate cancer (PCa) is a biologically heterogeneous disease, with a subset of cases driven by hereditary germline alterations. Targeted germline sequencing using the Twist Fixed Panel was performed in nine high-risk PCa patients (median age 47; range 30-61). Variants were classified based on ClinVar, gnomAD, and in silico prediction tools. Pathogenic and likely pathogenic variants in DNA damage repair (DDR) genes were identified, including BRCA2, BRIP1, PALB2, and BRCA1. A homozygous ATM variant was observed in one patient. Several ultra-rare variants in MLH3 and BARD1 were also detected. Most variants had allele frequencies <10-6. High-risk and early-onset PCa is associated with rare germline DDR alterations. These findings support expanded germline testing in younger patients and suggest potential relevance for precision oncology approaches, although functional validation is required..
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BibTeX
@article{hassan2026targeted,
title = {{Targeted Germline Sequencing Identifies Ultra-Rare DDR Variants in High-Risk Prostate Cancer : Short title: Germline DDR Variants in High-Risk Prostate Cancer.}},
author = {Rawaz Rizgar Hassan and Abdulkarim Yasin Karim},
journal = {Galen medical journal},
year = {2026},
month = aug,
doi = {10.31661/gmj.v15i.4248},
url = {https://europepmc.org/article/MED/42996496},
note = {CC BY},
}
RIS
TY - JOUR
TI - Targeted Germline Sequencing Identifies Ultra-Rare DDR Variants in High-Risk Prostate Cancer : Short title: Germline DDR Variants in High-Risk Prostate Cancer.
AU - Rawaz Rizgar Hassan
AU - Abdulkarim Yasin Karim
PY - 2026
DA - 2026/08/10
JO - Galen medical journal
DO - 10.31661/gmj.v15i.4248
UR - https://europepmc.org/article/MED/42996496
AB - Prostate cancer (PCa) is a biologically heterogeneous disease, with a subset of cases driven by hereditary germline alterations. Targeted germline sequencing using the Twist Fixed Panel was performed in nine high-risk PCa patients (median age 47; range 30-61). Variants were classified based on ClinVar, gnomAD, and in silico prediction tools. Pathogenic and likely pathogenic variants in DNA damage repair (DDR) genes were identified, including BRCA2, BRIP1, PALB2, and BRCA1. A homozygous ATM variant was observed in one patient. Several ultra-rare variants in MLH3 and BARD1 were also detected. Most variants had allele frequencies <10-6. High-risk and early-onset PCa is associated with rare germline DDR alterations. These findings support expanded germline testing in younger patients and suggest potential relevance for precision oncology approaches, although functional validation is required..
SN - 2588-2767
SN - 2322-2379
ER -