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RESEARCH PRODUCT

Predictive chromosomal clusters of synchronous and metachronous brain metastases in clear cell renal cell carcinoma

Ingmar BlümckeBastian GunawanRalf SchoberKathy KeyvaniMichael BuchfelderHenry W. S. SchroederLászló FüzesiMarlis GüntherHansdetlef WassmannMartin NischwitzWerner PaulusWolfgang StummerAlf GieseKlaus JungVeit RohdeJürgen MeixensbergerAngelika GutenbergAngelika GutenbergUlrich SureRupert EgenspergerChristina EndersJens BedkeWolfgang BrückRolf WarzokBjoern SanderPeter VajkoczyFrank Van LandeghemFrank Van LandeghemWolfgang FeidenMarkus BergmannDietmar Stolke

subject

AdultMaleCancer ResearchDNA Copy Number VariationsMedizinChromosome 9BiologySporadic Clear Cell Renal Cell Carcinoma03 medical and health sciences0302 clinical medicineGeneticsmedicineHumansCarcinoma Renal CellMolecular BiologyAgedRetrospective StudiesSequence Deletion030304 developmental biologyAged 80 and overChromosome AberrationsGeneticsComparative Genomic Hybridization0303 health sciencesBase SequenceBrain NeoplasmsChromosomeDNA NeoplasmMiddle Agedmedicine.diseaseKidney NeoplasmsClear cell renal cell carcinomaTumor progression030220 oncology & carcinogenesisCancer researchFemaleNeoplasm Recurrence LocalLow copy numberComparative genomic hybridizationBrain metastasis

description

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.

yearjournalcountryeditionlanguage
2014-05-17Cancer Genetics
https://doi.org/10.1016/j.cancergen.2014.05.004