The higher number of synchronous cases in cluster 1 was also associated with a significantly shorter RFS-BM compared with clusters 2 and 3 (P = 0.02). Cluster 2 cases had a high occurrence of -9p/-9q (94-98%) deletions, whereas cluster 3 cases had a higher frequency of copy number changes, including loss at chromosome 14 (80%). Correspondingly, k-means clustering showed that cluster 1 cases generally exhibited low copy number chromosomal changes that did not involve 3p. Losses at 9p and 9q appeared to be hallmarks of metachronous BM events, whereas an absence of detectable chromosomal changes at 3p was often associated with synchronous BM events. Using oncogenetic tree models and cluster analyses, chromosomal imbalances related to recurrence-free survival until BM (RFS-BM) were analyzed. Synchronous (early) and metachronous (late) brain metastasis (BM) events of sporadic clear cell renal cell carcinoma (ccRCC) (n = 148) were retrospectively analyzed using comparative genomic hybridization (CGH). 23 Stereology and Electron Microscopy Laboratory, Department of Clinical Medicine, Faculty of Health Sciences, Aarhus University, Aarhus, Denmark.22 Department of Neuropathology, Georg August University, Göttingen, Germany.21 Department of Neurosurgery, Georg August University, Göttingen, Germany.20 Department of Neurosurgery, Johannes Gutenberg University, Mainz, Germany.19 Department of Urology, Eberhard Karls University, Tübingen, Germany.18 Department of Pathology, Health Care Center Brandenburg, Brandenburg, Germany.17 Department of Neurosurgery, Charité University Medicine, Berlin, Germany.16 Department of Neuropathology, Charité University Medicine, Berlin, Germany Department of Neuropathology, University of Alberta, Edmonton, Canada.15 Department of Neurosurgery, University of Erlangen-Nürnberg, Erlangen, Germany.14 Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany.13 Department of Neurosurgery, Westphalian Wilhelm University, Münster, Germany.12 Department of Neuropathology, Westphalian Wilhelm University, Münster, Germany.11 Department of Neurosurgery, University of Leipzig, Leipzig, Germany.10 Department of Neuropathology, University of Leipzig, Leipzig, Germany.9 Department of Neuropathology, Ernst Moritz Arndt University, Greifswald, Germany.8 Department of Neurosurgery, Ernst Moritz Arndt University, Greifswald, Germany.
Electronic address: 2 Department of Gastroenteropathology, Georg August University, Göttingen, Germany. 1 Department of Neurosurgery, Georg August University, Göttingen, Germany Department of Neurosurgery, Johannes Gutenberg University, Mainz, Germany.