BRAF and KRAS mutations in prostatic adenocarcinoma

Abstract

Constitutive activation of the kinase cascade involving RAS, RAF, MEK and ERK is common to human cancers, and mutations of KRAS and BRAF are mutually exclusive and serve as alternatives to activate the RAS/RAF/ERK signaling pathway. RAS mutations are known to occur in prostate adenocarcinomas, but little is known about BRAF mutations in these tumors. In the present study, BRAF and KRAS mutations were characterized in 206 prostate adenocarcinomas by enhanced PCR-RFLP and direct sequencing. The identified KRAS and BRAF mutations were then analyzed with respect to preoperative serum PSA levels, Gleason scores and tumor stages. Mutations in codon 600 of BRAF were identified in 21 (10.2%) of 206 prostate adenocarcinomas. KRAS mutations in codons 12 or 13 were found in 15 (7.3%) of 206 prostate adenocarcinomas. However, no tumor specimen contained both BRAF and KRAS mutations. Prostate adenocarcinomas with a BRAF mutation tended to show higher preoperative serum PSA levels, Gleason scores and tumor stages than prostate adenocarcinomas with a KRAS mutation. The results obtained show that BRAF mutations are as uncommon as KRAS mutations in prostate adenocarcinoma. Although BRAF and KRAS are members of the same RAS/ERK signaling pathway, prostate adenocarcinomas with a BRAF mutation showed clinicopathologic features that differed from those of prostate adenocarcinoma with a KRAS mutation. ' 2006 Wiley-Liss, Inc.

PI3K signaling pathway is activated by PIK3CA mRNA overexpression and copy gain in prostate tumors, but PIK3CA, BRAF, KRAS and AKT1 mutations are infrequent events

“…KRAS mutations have been found in up to 8% of prostate tumors (see http://www.sanger.ac.uk/ genetics/CGP/cosmic/). [13][14][15][16] The first study on BRAF alterations in prostate cancer 18 revealed no mutations in the prostate adenocarcinomas of 17 Caucasian patients (0/17). The second study, in Asian patients, found a frequency of BRAF and KRAS mutation of 10 and 7%, respectively.…”

“…The second study, in Asian patients, found a frequency of BRAF and KRAS mutation of 10 and 7%, respectively. 16 Our series was made up of Caucasian patients and this could account for the lack of mutations in these genes. We confirmed this negative result for BRAF in a subset of cases by means of pyrosequencing.…”

“…[13][14][15][16] Two reports have been published about BRAF mutations in prostate tumors, but only Cho et al 16 described 10% of mutations in their Asian population. Most of BRAF mutations in human cancer consist in the missense mutation V600E 17 (see http://www.sanger.ac.uk/ genetics/CGP/cosmic/).…”

“…It has been reported that BRAF mutations occur in many tumor types in which KRAS is frequently mutated. 16,18 To date, only one article has reported AKT1 mutations in prostate cancer. Boormans et al 19 described the E17K change in 1 of 92 prostate tumors.…”

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

“…Oncogenic activating BRAF mutations were recently reported in approximately 10% of a series of 204 nonpretreated prostate cancer cases (5). This raises the possibility that BRAF inhibitors are a promising therapeutic option for androgen-independent prostate cancer patients in whom all current treatments have only limited efficacy.…”