Somatic mutations reveal complex metastatic seeding from multifocal primary prostate cancer.

Autor: Carm KT; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Johannessen B; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway., Bogaard M; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.; Department of Pathology, Oslo University Hospital-Radiumhospitalet, Oslo, Norway., Bakken AC; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway., Maltau AV; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway., Hoff AM; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway., Axcrona U; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.; Department of Pathology, Oslo University Hospital-Radiumhospitalet, Oslo, Norway., Axcrona K; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.; Department of Urology, Akershus University Hospital, Lørenskog, Norway., Lothe RA; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Skotheim RI; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.; Department of Informatics, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2023 Mar 01; Vol. 152 (5), pp. 945-951. Date of Electronic Publication: 2022 Aug 09.
DOI: 10.1002/ijc.34226
Abstrakt: Primary prostate cancer shows a striking intraorgan molecular heterogeneity, with multiple spatially separated malignant foci in the majority of patients. Metastatic prostate cancer, however, typically reveals more homogenous molecular profiles, suggesting a monoclonal origin of the metastatic lesions. Longitudinal mutational spectra, comparing multiple primary lesions with metastases from the same patients remain poorly defined. We have here analyzed somatic mutations in multisampled, spatio-temporal biobanked lesions (38 samples from primary foci and 1 sample from each of 8 metastases from seven prostate cancer patients) applying a custom-designed panel targeting 68 prostate cancer relevant genes. The metastatic samples were taken at time of primary surgery and up to 7 years later, and sampling included circulating tumor DNA in plasma or solid metastatic tissue samples. A total of 282 somatic mutations were detected, with a range of 0 to 25 mutations per sample. Although seven samples had solely private mutations, the remaining 39 samples had both private and shared mutations. Seventy-four percent of mutations in metastases were not found in any primary samples, and vice versa, 96% of mutations in primary cancers were not found in any metastatic samples. However, for three patients, shared mutations were found suggesting the focus of origin, including mutations in AKT1, FOXA1, HOXB13, RB1 and TP53. In conclusion, the spatio-temporal heterogeneous nature of multifocal disease is emphasized in our study, and underlines the importance of testing a recent sample in genomics-based precision medicine for metastatic prostate cancer.
(© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Databáze: MEDLINE
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