PuSH - Publication Server of Helmholtz Zentrum München: DNA-methylation and genomic copy number in primary tumors and corresponding lymph node metastases in prostate cancer from patients with low and high Gleason score.

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Unger, K. ; Hess J. ; Link, V.* ; Buchner, A.* ; Eze, C.* ; Li, M.* ; Stief, C.* ; Kirchner, T.* ; Klauschen, F.* ; Zitzelsberger, H. ; Niyazi, M.* ; Ganswindt, U.* ; Schmidt-Hegemann, N.S.* ; Belka, C.

DNA-methylation and genomic copy number in primary tumors and corresponding lymph node metastases in prostate cancer from patients with low and high Gleason score.

Clin. Transl. Radiat. Oncol. 39:100586 (2023)

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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.

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Purpose: In prostate cancer, the indication to irradiate the pelvic lymphatic pathways in clinical node-negative patients is solely based on clinical nomograms. To define biological risk patterns of lymphatic spread, we studied DNA-methylation and genomic copy number in primary tumors and corresponding lymph nodes metastases. Methods/Patients: DNA-methylation and genomic copy number profiles of primary tumors (PT) and paired synchronous lymph node metastases (LN) from Gleason Score (GS)-6/7a (n = 20 LN-positive, n = 20 LN-negative) and GS-9/10 patients (LN-positive n = 20) after prostatectomy and lymphonodectomy were analyzed. Results: GS-6/7a pN0 PTs and GS-6/7a pN1 PTs differed in histone H3K27me3/H3K9me3 mediated methylation. PTs compared to LNs, in both, GS-6/7a pN1 and GS-9/10 pN1 patients showed large differences in DNA-methylation mediated by histones H3K4me1/2, in addition to copy number changes of chromosomal regions 11q13.1, 14q11.2 and 15q26.1. Between GS-6/7a pN1 and GS-9/10 pN1 patients, methylation levels differed more when comparing LNs than PTs. 16q21-22.1 was specifically lost in GS-9/10 pN0 PTs. Immune system-related pathways characterized the differences between PTs and LNs in both GS-6/7a pN1 and GS-9/10 pN1 patients. Comparing PTs and LKs between GS-6/7a pN1 and GS-9/10 pN1 patients revealed altered transmembrane and G-protein-coupled receptor signaling. Conclusions: Our data suggest that progression of prostate cancer, including lymphatic spread, is associated with histone-mediated DNA-methylation and we hypothesize a methylation signature predicting lymphatic spread in GS-6/7a patients from primary tumors. Lymphatic spread in GS-6/7a patients, flanked by DNA-methylation and CNA alterations, appears to be more complex than in GS-9/10 patients, in whom the primary tumors already appear to bear lymph node metastasis-enabling alterations.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Dna-methylation ; Prostate Lymphatic Spread ; Signature; Long-term Survival; Radiation-therapy; Androgen Suppression; Pelvic Irradiation; High-risk; Radiotherapy; Neoadjuvant; Adenocarcinoma; Update

ISSN (print) / ISBN 2405-6308

e-ISSN 2405-6308

Journal Clinical and translational radiation oncology

Quellenangaben Volume: 39, Article Number: 100586

Publisher Elsevier

Publishing Place Amsterdam

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CCG Personalized Radiotherapy in Head and Neck Cancer (KKG-KRT)
Research Unit Radiation Cytogenetics (ZYTO)