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Frequent clonal relations between metastases and non-index prostate cancer lesions.

ABSTRACT: Primary prostate cancer lesions are clonally heterogeneous and often arise independently. In contrast, metastases were reported to share a monoclonal background. Because prostate cancer mortality is the consequence of distant metastases, prevention of metastatic outgrowth by primary tumor ablation is the main focus of treatment for localized disease. Focal therapy is targeted ablation of the primary index lesion, but it is unclear whether remaining primary lesions metastasize at a later stage. In this study, we compared copy number aberration profiles of primary prostate cancer lesions with matching pelvic lymph node metastases of 30 patients to establish clonality between a lymph node metastasis and multiple primary lesions within the same patient. Interestingly, in 23.3% of the cases, the regional metastasis was not clonally linked to the index primary lesion. These findings suggest that focal ablation of only the index lesion is potentially an undertreatment of a significant proportion of prostate cancer patients.

SUBMITTER: Kneppers J

PROVIDER: S-EPMC6413780 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Frequent clonal relations between metastases and non-index prostate cancer lesions.

Kneppers Jeroen J Krijgsman Oscar O Melis Monique M de Jong Jeroen J Peeper Daniel S DS Bekers Elise E van der Poel Henk G HG Zwart Wilbert W Bergman Andries M AM

JCI insight 20190124 2

Primary prostate cancer lesions are clonally heterogeneous and often arise independently. In contrast, metastases were reported to share a monoclonal background. Because prostate cancer mortality is the consequence of distant metastases, prevention of metastatic outgrowth by primary tumor ablation is the main focus of treatment for localized disease. Focal therapy is targeted ablation of the primary index lesion, but it is unclear whether remaining primary lesions metastasize at a later stage. I ...[more]

PMID: 30674724

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Project description:Brain metastases (BM) have been closely associated with increased morbidity and poor survival outcomes in patients with non‑small cell lung cancer (NSCLC). Excluding risk factors in histological subtypes, genomic alterations, including epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) rearrangements have been also regarded as greater risk factors for BM in the aspect of molecular subtypes. In the present study, 69 tumor tissues and 51 peripheral blood samples from patients with NSCLC were analyzed using a hybridization capture‑based next‑generation sequencing (NGS) panel, including 95 known cancer genes. Among the 90 patients with stage IV NSCLC, 26 cases suffered from BM and 64 cases did not. In total, 174 somatic mutations in 35 mutated genes were identified, and 12 of these genes were concurrently present in the BM group and the non‑BM group. Importantly, five mutated genes including ALK, cytidine deaminase (CDA), SMAD family member 4 (SMAD4), superoxide dismutase 2 (SOD2) and Von Hippel‑Lindau tumor suppressor (VHL) genes were uniquely detected in the BM group, and they were enriched in the Hippo signaling pathway, pyrimidine metabolism and pantothenate and co‑enzyme A (CoA) biosynthesis, as demonstrated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RNA polymerase II transcription regulator complex and promyelocytic leukemia nuclear body were the top functional categories according to the Gene Ontology enrichment analysis in the BM group and non‑BM group, respectively. Furthermore, 43.33% (13/30) of mutated genes were detected by both tumor tissue deoxyribonucleic acid (DNA) and plasma‑derived circulating tumor DNA (ctDNA) in the non‑BM group, while this percentage was only limited to 29.41% (5/17) in the BM group. To summarize, significant differences in somatic mutations, somatic interactions, key signaling pathways, functional biological information, and clinical actionability for the therapy of targeted agents were founded between the BM group and the non‑BM group, and ctDNA analysis may by applied as a more credible alternative for genomic profiling in patients with advanced NSCLC without BM, due to its higher consistency for genomic profiling between ctDNA analysis and tissue DNA analysis.

Dataset Information

Frequent clonal relations between metastases and non-index prostate cancer lesions.

Publications

Frequent clonal relations between metastases and non-index prostate cancer lesions.

Similar Datasets

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