Evolution of structural rearrangements in prostate cancer intracranial metastases.

Autor: Khani F; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA., Hooper WF; New York Genome Center, New York, NY, USA., Wang X; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA., Chu TR; New York Genome Center, New York, NY, USA., Shah M; New York Genome Center, New York, NY, USA., Winterkorn L; New York Genome Center, New York, NY, USA., Sigouros M; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA., Conteduca V; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.; Department of Medical and Surgical Sciences, Unit of Medical Oncology and Biomolecular Therapy, University of Foggia, Policlinico Riuniti, Foggia, Italy., Pisapia D; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA., Wobker S; Department of Pathology and Laboratory Medicine, UNC Chapel Hill, Chapel Hill, NC, USA., Walker S; Department of Medical Oncology, Oregon Health Sciences University, Portland, OR, USA., Graff JN; Department of Medical Oncology, Oregon Health Sciences University, Portland, OR, USA., Robinson B; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA., Mosquera JM; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA., Sboner A; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Elemento O; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA., Robine N; New York Genome Center, New York, NY, USA., Beltran H; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA. himisha_beltran@dfci.harvard.edu.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. himisha_beltran@dfci.harvard.edu.
Jazyk: angličtina
Zdroj: NPJ precision oncology [NPJ Precis Oncol] 2023 Sep 13; Vol. 7 (1), pp. 91. Date of Electronic Publication: 2023 Sep 13.
DOI: 10.1038/s41698-023-00435-3
Abstrakt: Intracranial metastases in prostate cancer are uncommon but clinically aggressive. A detailed molecular characterization of prostate cancer intracranial metastases would improve our understanding of their pathogenesis and the search for new treatment strategies. We evaluated the clinical and molecular characteristics of 36 patients with metastatic prostate cancer to either the dura or brain parenchyma. We performed whole genome sequencing (WGS) of 10 intracranial prostate cancer metastases, as well as WGS of primary prostate tumors from men who later developed metastatic disease (n = 6) and nonbrain prostate cancer metastases (n = 36). This first whole genome sequencing study of prostate intracranial metastases led to several new insights. First, there was a higher diversity of complex structural alterations in prostate cancer intracranial metastases compared to primary tumor tissues. Chromothripsis and chromoplexy events seemed to dominate, yet there were few enrichments of specific categories of structural variants compared with non-brain metastases. Second, aberrations involving the AR gene, including AR enhancer gain were observed in 7/10 (70%) of intracranial metastases, as well as recurrent loss of function aberrations involving TP53 in 8/10 (80%), RB1 in 2/10 (20%), BRCA2 in 2/10 (20%), and activation of the PI3K/AKT/PTEN pathway in 8/10 (80%). These alterations were frequently present in tumor tissues from other sites of disease obtained concurrently or sequentially from the same individuals. Third, clonality analysis points to genomic factors and evolutionary bottlenecks that contribute to metastatic spread in patients with prostate cancer. These results describe the aggressive molecular features underlying intracranial metastasis that may inform future diagnostic and treatment approaches.
(© 2023. Nature Publishing Group UK.)
Databáze: MEDLINE
Externí odkaz: