title: Clinical relevance of loss of 11p15 in primary and metastatic breast cancer: association with loss of PRKCDBP expression in brain metastases.
abstract: The occurrence of brain metastases among breast cancer patients is currently rising with approximately 20-25% incidence rates, underlining the importance of the identification of new therapeutic and prognostic markers. We have previously screened for new markers for brain metastasis by array CGH. We found that loss of 11p15 is common among these patients. In this study, we investigated the clinical significance of loss of 11p15 in primary breast cancer (BC) and breast cancer brain metastases (BCBM). 11p15 aberration patterns were assessed by allelic imbalance (AI) analysis in primary BC (n = 78), BCBM (n = 21) and metastases from other distant sites (n = 6) using six different markers. AI at 11p15 was significantly associated with BCBM (p = 0.002). Interestingly, a subgroup of primary BC with a later relapse to the brain had almost equally high AI rates as the BCBM cases. In primary BC, AI was statistically significantly associated with high grade, negative hormone receptor status, and triple-negative (TNBC) tumors. Gene expression profiling identified PRKCDBP in the 11p15 region to be significantly downregulated in both BCBM and primary BC with brain relapse compared to primary tumors without relapse or bone metastasis (fdr<0.05). qRT-PCR confirmed these results and methylation was shown to be a common way to silence this gene. In conclusion, we found loss at 11p15 to be a marker for TNBC primary tumors and BCBM and PRKCDBP to be a potential target gene in this locus.
authors.affiliation: Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. hwikman@uke.de
authors.forename: Harriet
authors.initials: H
authors.lastname: Wikman
authors.forename: Bettina
authors.initials: B
authors.lastname: Sielaff-Frimpong
authors.forename: Jolanthe
authors.initials: J
authors.lastname: Kropidlowski
authors.forename: Isabell
authors.initials: I
authors.lastname: Witzel
authors.forename: Karin
authors.initials: K
authors.lastname: Milde-Langosch
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.forename: Katrin
authors.initials: K
authors.lastname: Lamszus
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012008:Recurrence
chemical_list: D014408:Biomarkers, Tumor; C505360:CAVIN3 protein, human; D047908:Intracellular Signaling Peptides and Proteins