Advances in Clinical and Experimental Medicine

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Advances in Clinical and Experimental Medicine

2012, vol. 21, nr 6, November-December, p. 821–829

Publication type: review article

Language: English

Genetic Aspects of Pheochromocytoma

Genetyczne aspekty guza chromochłonnego

Katarzyna Kolačkov1,A,B,C,D,E,F, Krzysztof Tupikowski2,A,C,E,F, Grażyna Bednarek-Tupikowska1,A,C,D,E,F

1 Department of Endocrinology, Diabetology and Isotope Therapy, Wroclaw Medical University, Wroclaw, Poland

2 Department of Urology and Urological Oncology, Wroclaw Medical University, Wroclaw, Polan

Abstract

Pheochromocytomas are derived from chromaffin cells of the adrenal medulla which synthesize and secrete catecholamines, thus affecting the cardiovascular system and metabolic processes. Pheochromocytoma is a tumor of the following multicarcinoma hereditary syndromes: type 2 multiple endocrine neoplasia, von Hippel-Lindau disease, type 1 neurofibromatosis and the pheochromocytomas/paragangliomas syndrome. Pheochromocytomas are relatively rare, and because of non-specific manifestation of these tumors and the possible lack of signs and symptoms for extended periods of time, the diagnosis may be delayed, which may, in turn, lead to death. Pheochromocytomas may occur sporadically. However, due to the frequent incidence of hereditary forms of these cancers, the presymptomatic genetic testing of family members with a positive family history is indicated, thus allowing for selecting people with higher risk of cancer. Early detection of the syndrome and the coexisting tumors (which may be malignant) may lead to a correct diagnosis, regular surveillance, preventive examinations and implementation of appropriate early treatment. Recent examinations have shown significant involvement of RET, VHL, NF1, SDHB and SDHD as well as the newly discovered KIF1Bβ, TMEM127 and MAX genes in pathogenesis of these tumors. The microarray-gene expression studies, based on the analysis of cellular pathways, have revealed two distinct clusters indicating two different routes of tumorgenesis. The genotype-phenotype correlations are still being studied and future research can give us clearer information about the function of these genes, which may prove crucial from the clinical point of view.

Streszczenie

Guzy chromochłonne wywodzą się z komórek chromochłonnych rdzenia nadnerczy, które syntetyzują i wydzielają katecholaminy, przez co wpływają na układ krążenia i procesy metaboliczne. Guzy chromochłonne wchodzą w skład dziedzicznych zespołów nowotworowych, takich jak: zespół mnogiej gruczolakowatości wewnątrzwydzielniczej typu 2, choroba von Hippel-Lindau, nerwiakowłókniakowatość typu 1 oraz zespół guza chromochłonnego i przyzwojaków. Diagnoza guza chromochłonnego może być utrudniona ze względu na jego stosunkowo rzadkie występowanie, mało specyficzne objawy oraz możliwy ich brak przez dłuższy okres. Brak odpowiedniego rozpoznania może prowadzić nawet do śmierci pacjenta. Guzy chromochłonne mogą występować sporadycznie, jednak ze względu na częste występowanie rodzinnej formy tych nowotworów, jest wskazane przeprowadzanie przedobjawowych badań genetycznych w celu wczesnego wykrycia choroby, szczególnie wśród krewnych pierwszego stopnia. Diagnostyka genetyczna pozwala na objęcie chorych z grupy ryzyka odpowiednimi badaniami profilaktycznymi, których celem jest wczesne wykrycie zespołu i współistniejących nowotworów (niektóre z nich mogą być złośliwe), kontrolę stanu zdrowia pacjenta i wdrożenie odpowiedniego wczesnego leczenia. Ostatnie badania wykazały znaczący udział genów, takich jak: RET, VHL, NF1, SDHB i SDHD, jak również udział nowo odkrytych genów: KIF1Bβ, TMEM127 i MAX w patogenezie tych nowotworów. Badania ekspresji genów (z wykorzystaniem mikromacierzy) na podstawie analizy szlaków komórkowych ujawniły dwa klastry wskazujące dwie różne drogi nowotworzenia. Korelacje genotyp-fenotyp są wciąż w fazie badań, a przyszłe doniesienia mogą dać więcej informacji na temat funkcji tych genów, co może być istotne z klinicznego punktu widzenia.

Key words

pheochromocytoma, paraganglioma, hereditary syndromes, genes

Słowa kluczowe

guz chromochłonny, przyzwojaki, zespoły dziedziczne, geny, mutacje

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