PMID- 20139910 OWN - NLM STAT- MEDLINE DCOM- 20100615 LR - 20230210 IS - 1530-0285 (Electronic) IS - 0893-3952 (Linking) VI - 23 IP - 4 DP - 2010 Apr TI - Amplification of 8q21 in breast cancer is independent of MYC and associated with poor patient outcome. PG - 603-10 LID - 10.1038/modpathol.2010.5 [doi] AB - Copy number gains involving the long arm of chromosome 8, including high-level amplifications at 8q21 and 8q24, have been frequently reported in breast cancer. Although the role of the MYC gene as the driver of the 8q24 amplicon is well established, the significance of the 8q21 amplicon is less clear. The breast cancer cell line SK-BR-3 contains three separate 8q21 amplicons, the distal two of which correspond to putative target genes TPD52 and WWP1. To understand the effect of proximal 8q21 amplification on breast cancer phenotype and patient prognosis, we analyzed 8q21 copy number changes using fluorescence in situ hybridization (FISH) in a tissue microarray containing more than 2000 breast cancers. Amplification at 8q21 was found in 3% of tumors, and was associated with medullary type (P<0.03), high tumor grade (P<0.0001), high Ki67 labeling index (P<0.05), amplification of MYC (P<0.0001), HER2, MDM2, and CCND1 (P<0.05 each), as well as the total number of gene amplifications (P<0.0001). 8q21 copy number gains were significantly related to unfavorable patient outcome in univariate analysis. However, multivariate Cox regression analysis did not reveal an independent prognostic value of 8q21 amplification. The position of our FISH probe and data of a previously performed high-resolution CGH study in the breast cancer cell line SK-BR-3 involve TCEB1 and TMEM70 as new possible candidate oncogenes at 8q21 in breast cancer. FAU - Choschzick, Matthias AU - Choschzick M AD - Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. mchoschz@uke.uni-hamburg.de FAU - Lassen, Paula AU - Lassen P FAU - Lebeau, Annette AU - Lebeau A FAU - Marx, Andreas Holger AU - Marx AH FAU - Terracciano, Luigi AU - Terracciano L FAU - Heilenkotter, Uwe AU - Heilenkotter U FAU - Jaenicke, Fritz AU - Jaenicke F FAU - Bokemeyer, Carsten AU - Bokemeyer C FAU - Izbicki, Jakob AU - Izbicki J FAU - Sauter, Guido AU - Sauter G FAU - Simon, Ronald AU - Simon R LA - eng PT - Journal Article DEP - 20100205 PL - United States TA - Mod Pathol JT - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JID - 8806605 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Breast Neoplasms/*genetics/mortality/*pathology MH - Chromosomes, Human, Pair 8/*genetics MH - Drug Resistance, Neoplasm/genetics MH - Female MH - Gene Amplification MH - Gene Dosage MH - Genes, myc MH - Humans MH - In Situ Hybridization, Fluorescence MH - Kaplan-Meier Estimate MH - Middle Aged MH - Prognosis MH - Tissue Array Analysis MH - Treatment Outcome EDAT- 2010/02/09 06:00 MHDA- 2010/06/16 06:00 CRDT- 2010/02/09 06:00 PHST- 2010/02/09 06:00 [entrez] PHST- 2010/02/09 06:00 [pubmed] PHST- 2010/06/16 06:00 [medline] AID - S0893-3952(22)02740-5 [pii] AID - 10.1038/modpathol.2010.5 [doi] PST - ppublish SO - Mod Pathol. 2010 Apr;23(4):603-10. doi: 10.1038/modpathol.2010.5. Epub 2010 Feb 5.