Rare Genetic Drivers of Lethal Prostate Cancer
Menée à partir de données de séquençage génomique portant sur 17 546 hommes atteints d'un cancer de la prostate et d'ascendance européenne, cette étude met en évidence une association entre des variants situés au niveau de gènes impliqués dans la réparation de l'ADN ou au niveau de gènes de susceptibilité au cancer et l'agressivité de la tumeur
Genetic testing is a recently adopted standard of care for male patients with metastatic or high-risk localized prostate cancer. Rare deleterious germline alterations in a small number of cancer-associated genes are relevant for clinical management and/or selection of systemic therapy. The most well-known prostate cancer predisposition gene is BRCA2, with deleterious germline BRCA2 variants strongly associated with poor prognosis across the spectrum of disease, and also conferring sensitivity to poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in the metastatic castration-resistant setting. The genes TP53, ATM, MSH2, and several other genes directly or indirectly linked with DNA damage repair processes are also associated with clinically-aggressive prostate cancer and/or response to PARP inhibitors or immune checkpoint inhibitors.
JAMA Oncology , éditorial, 2022