Naslov
Genetic profiling of neuroendocrine tumours insulinomas and pheochromocytomas

Autori
Hrašćan, Reno ; Pećina-Šlaus, Nives ; Ozretić, Luka ; Bulić-Jakuš, Floriana ; Franekić Čolić, Jasna

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts of the Second Congress of Croatian Geneticists with international participation / Franekić Čolić, Jasna ; Ugarković, Đurđica - Zagreb, 2005, 50-50

Skup
Congress of Croatian Geneticists with international participation (2 ; 2005)

Mjesto i datum
Brač, Hrvatska, 24.09.2005. - 27.09.2005

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
pheochromocytomas; insulinomas; oncogenes; tumor-suppressor genes; point mutations; loss of heterozygosity; allelic imbalance; replication error positive samples

Sažetak
Pheochromocytomas and insulinomas are neuroendocrine tumours located in the adrenal medulla and pancreatic inslets. They both may be either sporadic or manifestation of a familial cancer syndromes. In the present study different genes were investigated in human pheochromocytomas and insulinomas. Genetic changes of ret, K-ras, NF-1, p53, nm23-H1, BRCA-1, APC and CDH1 were tested for point mutations and loss of heterozygosity (LOH). Fifteen sporadic pheochromocytomas and 22 insulinomas were analysed by PCR using Restriction Fragment Length Polymorphism method. The results of our analysis showed two pheochromocytomas with point mutations of the ret. Point mutations of K-ras were very frequent: 62% of pheochromocytomas and 50% of insulinomas harboured K-ras mutations. Only one insulinoma out of 5 informative showed LOH of NF-1 and another insulinoma out of 6 informative showed LOH of p53. Allelic loss of nm23-H1 was detected in one insulinoma and two other insulinomas showed LOH of BRACA-1. One allelic imbalance of the APC out of 11 heterozygous pheochromocytomas and one allelic imbalance of the CDH1 out of 13 heterozygous pheochromocytomas were detected. Our marker revealed another type of genomic instability, characteristic of tumour cells-replication error positive samples (RER+). Four out of 13 heterozygous pheochromocytomas were RER+. Our results suggest that alterations of different genes components of specific signalling pathways are responsible for neuroendocrine tumour formation. Frequent mutations found in K-ras suggests that signalling pathway RAS-RAF-ERK plays a role in insulinoma and pheoechromocytoma development. Allelic imbalances of APC and CDH1, suggest that wnt pathway may have a role in pheochromocytoma.

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija

POVEZANOST RADA