title: Predictive chromosomal clusters of synchronous and metachronous brain metastases in clear cell renal cell carcinoma.
abstract: 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). Using oncogenetic tree models and cluster analyses, chromosomal imbalances related to recurrence-free survival until BM (RFS-BM) were analyzed. 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. Correspondingly, k-means clustering showed that cluster 1 cases generally exhibited low copy number chromosomal changes that did not involve 3p. 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%). 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). Conversely, a significantly longer RFS-BM was observed for cluster 2 versus clusters 1 and 3 (P = 0.02). Taken together, these data suggest that metachronous BM events of ccRCC are characterized by loss of chromosome 9, whereas synchronous BM events may form independently of detectable genetic changes at chromosomes 9 and 3p.
authors.affiliation: Department of Neurosurgery, Georg August University, Göttingen, Germany; Department of Neurosurgery, Johannes Gutenberg University, Mainz, Germany. Electronic address: agutenberg@uni-mainz.de.
authors.forename: Angelika
authors.initials: A
authors.lastname: Gutenberg
authors.affiliation: Department of Gastroenteropathology, Georg August University, Göttingen, Germany.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Nischwitz
authors.affiliation: Department of Gastroenteropathology, Georg August University, Göttingen, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Gunawan
authors.affiliation: Department of Gastroenteropathology, Georg August University, Göttingen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Enders
authors.affiliation: Department of Medical Statistics, Georg August University, Göttingen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.affiliation: Department of Neuropathology, Klinikum Bremen-Mitte, Bremen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bergmann
authors.affiliation: Departments of Gastroenteropathology and Neuropathology, University of the Saarland, Homburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Feiden
authors.affiliation: Institute of Neuropathology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Egensperger
authors.affiliation: Institute of Neuropathology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Kathy
authors.initials: K
authors.lastname: Keyvani
authors.affiliation: Department of Neurosurgery, University of Duisburg-Essen, Essen, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Stolke
authors.affiliation: Department of Neurosurgery, University of Duisburg-Essen, Essen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sure
authors.affiliation: Department of Neurosurgery, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: Henry W S
authors.initials: HW
authors.lastname: Schroeder
authors.affiliation: Department of Neuropathology, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Warzok
authors.affiliation: Department of Neuropathology, University of Leipzig, Leipzig, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schober
authors.affiliation: Department of Neurosurgery, University of Leipzig, Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Meixensberger
authors.affiliation: Department of Neuropathology, Westphalian Wilhelm University, Münster, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.affiliation: Department of Neurosurgery, Westphalian Wilhelm University, Münster, Germany.
authors.forename: Hansdetlef
authors.initials: H
authors.lastname: Wassmann
authors.affiliation: Department of Neurosurgery, Westphalian Wilhelm University, Münster, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stummer
authors.affiliation: Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Blumcke
authors.affiliation: Department of Neurosurgery, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Buchfelder
authors.affiliation: Department of Neuropathology, Charité University Medicine, Berlin, Germany; Department of Neuropathology, University of Alberta, Edmonton, Canada.
authors.forename: Frank K H
authors.initials: FK
authors.lastname: van Landeghem
authors.affiliation: Department of Neurosurgery, Charité University Medicine, Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Vajkoczy
authors.affiliation: Department of Pathology, Health Care Center Brandenburg, Brandenburg, Germany.
authors.forename: Marlis
authors.initials: M
authors.lastname: Günther
authors.affiliation: Department of Urology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Bedke
authors.affiliation: Department of Neurosurgery, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Alf
authors.initials: A
authors.lastname: Giese
authors.affiliation: Department of Neurosurgery, Georg August University, Göttingen, Germany.
authors.forename: Veit
authors.initials: V
authors.lastname: Rohde
authors.affiliation: Department of Neuropathology, Georg August University, Göttingen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.affiliation: Department of Gastroenteropathology, Georg August University, Göttingen, Germany.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Füzesi
authors.affiliation: Stereology and Electron Microscopy Laboratory, Department of Clinical Medicine, Faculty of Health Sciences, Aarhus University, Aarhus, Denmark.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Sander
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000556:secondary*; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D012189:Retrospective Studies; D017384:Sequence Deletion
chemical_list: D004273:DNA, Neoplasm
keywords: Clear cell renal cell carcinoma; brain metastasis; chromosomal copy number alterations; comparative genomic hybridization (CGH); tumor progression