Mutations of the BRAF gene in squamous cell carcinoma of the head and neck.
The RAF/MEK/ERK (MAPK) signal transduction cascade is an important mediator of a number of cellular fates including growth, proliferation and survival. The BRAF gene, one of the human isoforms of RAF, is activated by oncogenic RAS, leading to cooperative effects in cells responding to growth factor signals. This study was performed to elucidate a possible function of BRAF in squamous cell carcinoma of the head and neck (HNSCC). Mutations of BRAF and KRAS2 were evaluated in 89 HNSCC and corresponding normal mucosa by direct DNA sequencing analyses after microdissection. The results obtained were correlated with histopathological variables. Activating BRAF missense mutations were identified in 3/89 HNSCC (3%). KRAS2 mutations were found in five out of 89 (6%) HNSCC examined. There were no mutations of KRAS2 and BRAF in non-neoplastic mucosa. We failed to observe a correlation between BRAF or KRAS2 mutations and histopathological factors. Our data indicate that BRAF gene mutations are relatively rare events in HNSCC. Although uncommon, BRAF mutations may identify a subset of patients with HNSCC sensitive to targeted therapy.
Weber
Anette
A
Department of Otorhinolaryngology, Head and Neck Surgery, University of Leipzig, Liebigstrasse 18a, 04103 Leipzig, Germany.
Langhanki
Larissa
L
Sommerer
Florian
F
Markwarth
Annett
A
Wittekind
Christian
C
Tannapfel
Andrea
A
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002455:Cell Division; D002470:Cell Survival; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D009154:Mutation; D020125:Mutation, Missense; D015513:Oncogene Proteins / Q000235:genetics*; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D018631:ras Proteins
C117307:KRAS protein, human; D015513:Oncogene Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins