OBJECTIVES: A dysregulated mitogen-activated protein kinase (MAPK) pathway plays an important role in various malignancies and is often mediated by mutations in several oncogenes (eg, RAF, RAS). B-RAF mutations, predominantly the specific V600E mutation and additional alterations in exons 11 and 15, were frequently detected in malignant melanomas, papillary thyroid tumors, and colorectal cancers with microsatellite instability (MSI). The present study investigated B-RAF mutations, MSI status, and activation of MAPK signaling in prostate tumors. METHODS: The V600E mutation of the B-RAF gene was analyzed using allele-specific polymerase chain reaction in 79 archival prostatic adenocarcinomas (pT1aG1 to pT3cG3, median Gleason score 6); exons 11 and 15 were sequenced. MSI status was determined using the National Cancer Institute consensus panel for hereditary nonpolyposis colorectal carcinoma (HNPCC) detection. Active MAPK signaling was investigated using immunohistochemistry for p44/ERK1 and p42/ERK2. RESULTS: No B-RAF mutations could be detected. Six of 79 tumors showed MSI positivity. Active MAPK signaling was detected in 51% of the analyzed tumors. No correlation was found between MAPK activity and histopathologic/clinical characteristics. CONCLUSION: The most frequent B-RAF gene alterations are not involved in prostate carcinogenesis. MSI is infrequent in prostate cancer and is not linked to B-RAF mutations. MAPK signaling is frequently activated in prostate tumors and might be suitable for a therapeutic approach.
OBJECTIVES: A dysregulated mitogen-activated protein kinase (MAPK) pathway plays an important role in various malignancies and is often mediated by mutations in several oncogenes (eg, RAF, RAS). B-RAF mutations, predominantly the specific V600E mutation and additional alterations in exons 11 and 15, were frequently detected in malignant melanomas, papillary thyroid tumors, and colorectal cancers with microsatellite instability (MSI). The present study investigated B-RAF mutations, MSI status, and activation of MAPK signaling in prostate tumors. METHODS: The V600E mutation of the B-RAF gene was analyzed using allele-specific polymerase chain reaction in 79 archival prostatic adenocarcinomas (pT1aG1 to pT3cG3, median Gleason score 6); exons 11 and 15 were sequenced. MSI status was determined using the National Cancer Institute consensus panel for hereditary nonpolyposis colorectal carcinoma (HNPCC) detection. Active MAPK signaling was investigated using immunohistochemistry for p44/ERK1 and p42/ERK2. RESULTS: No B-RAF mutations could be detected. Six of 79 tumors showed MSI positivity. Active MAPK signaling was detected in 51% of the analyzed tumors. No correlation was found between MAPK activity and histopathologic/clinical characteristics. CONCLUSION: The most frequent B-RAF gene alterations are not involved in prostate carcinogenesis. MSI is infrequent in prostate cancer and is not linked to B-RAF mutations. MAPK signaling is frequently activated in prostate tumors and might be suitable for a therapeutic approach.
Authors: M Burger; A Hartmann; R Stoehr; F Hofstaedter; B Kneitz; H Riedmiller; W F Wieland; S Denzinger Journal: Urologe A Date: 2007-09 Impact factor: 0.639
Authors: Janice M Mehnert; Antoinette R Tan; Rebecca Moss; Elizabeth Poplin; Mark N Stein; Mika Sovak; Kelly Levinson; Hongxia Lin; Michael Kane; Murugesan Gounder; Yong Lin; Weichung Joe Shih; Eileen White; Eric H Rubin; Vassiliki Karantza Journal: Mol Cancer Ther Date: 2011-06-16 Impact factor: 6.261
Authors: Manish I Patel; Jaskirat Singh; Marzieh Niknami; Caroline Kurek; Mu Yao; Sasa Lu; Fiona Maclean; Nicholas J C King; Michael H Gelb; Kieran F Scott; Pamela J Russell; John Boulas; Qihan Dong Journal: Clin Cancer Res Date: 2008-12-15 Impact factor: 12.531
Authors: Kimberly D P Hammer; James D Alsop; Rita A Buresh-Stiemke; Katsiaryna Frantskevich; Rita L Malinowski; Laura S Roethe; Ginny L Powers; Paul C Marker Journal: Prostate Date: 2014-03-20 Impact factor: 4.104
Authors: Martin H Hager; Samantha Morley; Diane R Bielenberg; Sizhen Gao; Matteo Morello; Ilona N Holcomb; Wennuan Liu; Ghassan Mouneimne; Francesca Demichelis; Jayoung Kim; Keith R Solomon; Rosalyn M Adam; William B Isaacs; Henry N Higgs; Robert L Vessella; Dolores Di Vizio; Michael R Freeman Journal: EMBO Mol Med Date: 2012-05-16 Impact factor: 12.137
Authors: Electa R Park; Ashok K Pullikuth; Evangeline M Bailey; Donald E Mercante; Andrew D Catling Journal: Cell Commun Signal Date: 2009-11-23 Impact factor: 5.712
Authors: Xing-Dong Feng; Shu-Guang Huang; Jian-Yong Shou; Bi-Rong Liao; Jonathan M Yingling; Xiang Ye; Xi Lin; Lawrence M Gelbert; Eric W Su; Jude E Onyia; Shu-Yu Li Journal: Genomics Proteomics Bioinformatics Date: 2007-02 Impact factor: 7.691