Activating BRAF gene mutations are uncommon in hormone refractory prostate cancer in Caucasian patients

Abstract

Abstract. Activating mutations in the cytosolic serine/ threonine kinase, BRAF, have been reported in a variety of neoplasms. BRAF activation may contribute to tumor growth via activation of the MAP/ERK kinase pathway, and BRAF represents a possible therapeutic target. Activating BRAF mutations were recently reported in approximately 10% of prostate cancer cases in Asian patients. In the present study, 43 hormone refractory prostate cancers were analyzed for BRAF mutations in order to determine whether anti-BRAF therapy is a suitable approach for advanced prostate cancer patients. In all of the studied tumors, BRAF exons 11 and 15 were PCR-amplified and sequenced, including the backward and forward sequences. BRAF mutations were noted only in the positive control tissues, but were not found in any of the 43 analyzed prostate cancers. We conclude that BRAF mutations occur only rarely in prostate cancers in Caucasian patients and are not associated with tumor progression. The application of anti-BRAF therapies may therefore not be beneficial for prostate cancer.

Targeting BRAF-Mutant Non-Small Cell Lung Cancer: From Molecular Profiling to Rationally Designed Therapy

“…Differences in the frequency of BRAF mutations based on ethnicity have been observed in other tumor types, including a higher incidence of BRAF ‐mutant colorectal cancer in patients of Anglo‐Saxon descent versus Southern European descent. In prostate cancer, BRAF mutations have been identified in Asian patients but not in white patients . Data are limited in NSCLC, but studies suggest that BRAF mutations may occur at a lower frequency in Asian patients (0.8%–2.0%) compared with white patients primarily from France and the U.S. (2%–4%) .…”

CDCP1 overexpression drives prostate cancer progression and can be targeted in vivo

“…Interestingly, activation of the MAPK pathway by K-RAS in a PTEN-deficient prostate cancer mouse model leads to the development of metastatic prostate cancer (8). However, mutations of either KRAS or BRAF account for only a minority of human prostate cancer cases (5,9,10). Thus, the identification of new regulators of this pathway, in the context of PTEN-null prostate cancers, would open the way to new effective therapies for the treatment of this disease.…”

Nachweis der BRAF-Mutation bei kaninen Prostataerkrankungen

“…Forscher aus den USA untersuchten in Neoplasien des Hundes die BRAF-Variante V595E (cBRAF-Referenzsequenz ENSCAFT00000006306), die der humanen BRAF-Variante V600E entspricht, und identifizierten die Mutation in Tumorzellen von 80 % der 25 untersuchten kaninen PCa [25]. Im Gegensatz dazu wird das PCa des Menschen nur selten durch die BRAF-Mutation verursacht [17] [22].…”