role of kcnma1 in breast cancerkcnma1在乳腺癌的作用.pdfVIP

Role of KCNMA1 in Breast Cancer 1 2 1 1 3 1 Martin Oeggerli *, Yuemin Tian , Christian Ruiz , Barbara Wijker , Guido Sauter , Ellen Obermann , ¨ 4 5 6 2 1 Uwe Guth , Inti Zlobec , Matthias Sausbier , Karl Kunzelmann , Lukas Bubendorf 1 Institute of Pathology, University of Basel, Basel, Switzerland, 2 Institute of Physiology, University of Regensburg, Regensburg, Germany, 3 Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 4 Department of Gynecology and Obstetrics, University Hospital Basel, Basel, Switzerland, 5 Institute ¨ ¨ of Pathology, University of Bern, Bern, Switzerland, 6 Institute of Pharmacy, University of Tubingen, Tubingen, Germany Abstract KCNMA1 encodes the a-subunit of the large conductance, voltage and Ca2+-activated (BK) potassium channel and has been reported as a target gene of genomic amplification at 10q22 in prostate cancer. To investigate the prevalence of the amplification in other human cancers, the copy number of KCNMA1 was analyzed by fluorescence-in-situ-hybridization (FISH) in 2,445 tumors across 118 different tumor types. Amplification of KCNMA1 was restricted to a small but distinct fraction of breast, ovarian and endometrial cancer with the highest prevalence in invasive ductal breast cancers and serous carcinoma of ovary and endometrium (3–7%). We performed an extensive analysis on breast cancer tissue microarrays (TMA) of 1,200 tumors linked to prognosis. KCNMA1 amplification was signific