Absence of microsatellite instability and BRAF (V600E) mutation in testicular germ cell tumors.

Testicular germ cell tumors (TGCT) are the most common malignant neoplasm in young men. DNA mismatch repair deficiency can lead to microsatellite instability (MSI), an important mechanism of genetic instability. A mutation of the BRAF gene has been implicated in the pathogenesis of several solid tumors and has recently become an important therapeutic target. The role of MSI and BRAF gene mutation in TGCT, particularly in refractory disease, is poorly understood and reported findings are controversial. In this study, we aimed to determine the frequency and clinical impact of MSI status and BRAF mutations in TGCT. DNA was isolated from formalin-fixed paraffin embedded (FFPE) tissue from 150 TGCT cases. The MSI phenotype was evaluated using multiplex PCR for five quasimonomorphic mononucleotide repeat markers. Exon 15 of the BRAF oncogene (V600E) was analyzed by PCR, followed by direct sequencing. Sixteen percent of cases were considered to have refractory disease. In a small subset of cases (17 for MSI and 18 for BRAF), the quantity and quality of DNA recovery were poor and therefore, were unable to be analyzed. The remaining 133 TGCT cases showed a complete absence of MSI. Of the 132 cases successfully evaluated for BRAF mutations, all were V600E wild-type. In conclusion, despite a distinct response of testicular germ cell tumors to therapy, microsatellite instability, and the BRAF V600E mutation were absent in all testicular germ cell tumors tested in this study.

KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy.

Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Adenoma is the main precursor lesion and, recently, the serrated polyps were described as a group of colorectal lesions with malignant potential. The morphologic and biologic characterizations of serrated polyps remain limited. The aim of the present study was to determine the frequency of KRAS and BRAF mutations and microsatellite instability (MSI) in CRC precursor lesions, to evaluate the association between molecular, pathologic and morphologic alterations in precursor lesions and to compare with the alterations detected in CRC. A series of 342 precursor lesions were removed from 155 patients during colonoscopy. After morphologic classification, molecular analysis was performed in 103 precursor lesions, and their genetic profile compared with 47 sporadic CRCs. Adenomas were the main precursor lesions (70.2%). Among the serrated polyps, the main precursor lesion was hyperplastic polyps (HPs) (82.4%), followed by sessile serrated adenomas (12.7%) and traditional serrated adenomas (2.0%). KRAS mutations were detected in 13.6% of the precursor lesions, namely in adenomas and in HPs, but in no serrated adenoma. BRAF mutations were found in 9 (8.7%) precursor lesions, mainly associated with serrated polyps and absent in adenomas (P<0.001). High MSI (MSI-H) was absent in precursor lesions. In the 47 CCR cases, 46.8% exhibited KRAS mutation, 6.5% BRAF mutations and 10.6% MSI-H. This study confirms the role of KRAS and BRAF mutations in CRC carcinogenesis, a crucial step in implementing CRC screening strategies.