The RAF-MEK-ERK is an important signaling pathway that controls cellular proliferation, differentiation and survival. Recent reports indicate that R-RAF is mutated at a high frequency in human cancer. The mutations are clustered in the glycine-rich loop and activation segment which are encoded by exon 11 and exon 15, respectively. Among these mutations, V600E is the most prevalent found in varieties of human cancers, include melanoma and thyroid carcinomas. In this thesis, we analyzed 86 human cancer specimens, including 62 lung cancers and 24 esophageal cancers, for the mutation of exons 11 and 15 by PCR and direct DNA sequencing. However, we can not detect any mutation in these two exons in these clinical samples, these results suggest indicating that BRAF mutation might be rare and analysis of larger sample size is needed to confirmed this conclusion.

This work summarizes the results of a research inquiring into relatively rare neuroendocrine tumors - pheochromocytomas and paragangliomas (PHEO/PGL) These tumors may arise on a hereditary genetic predisposition basis. On that account we primarily focused on a genetic examination of patients with PHEO/PGL. Methods for diagnostics of changes in SDHD, SDHB and RET genes were implemented. The number of examined genes has been (and is still being) extended. Currently we are investigating these genes: ATRX, BRAF, CDH1, CDKN2A, CDKN2B, FGFR1, FH, FHIT, GNAS, HIF2A (EPAS1), H-RAS, IDH1, IDH2, KIF1Bß, KMT2D, K-RAS, MAML3, MAX, MDH2, MET, NF1, NGFR, N-RAS, PHD2/EGLN1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TERT, TMEM 127, TP53 and VHL, using next generation sequencing. The number of variations of the above mentioned genes is different (23%) in Czech patients with PHEO/PGL in comparison with some foreign studies (27%, 40%). This may be caused by geographical influences or selection of patients. PHEO/PGL occur mainly (75%) in a benign form. A malignant form may be indicated by the presence of chromaffin tissue in locations where these tumors do not usually occur - liver, lungs, bones. In our study we focused on characteristics indicating the malignancy, for example, the lower age of patients with the first manifestation...