Molecular mechanisms of development of basal-cell carcinoma associated with hereditary syndromes

Abstract

New data on the pathogenetic mechanisms leading to the development of epithelial neoplasm of the skin, such as Hedgehog and Wnt signal pathways, were obtained recently. Impairments of the molecular mechanisms in these signal pathways were detected for the first time in some hereditary diseases and various tumors, including cutaneous basal-cell carcinoma. It was for the first time revealed that Hedgehog and Wnt signaling regulated the activities of the main genes involved in the morphogenesis processes. Gorlin-Goltz genetic syndrome is associated with early development of basal-cell cutaneous cancer. The genetic base and the molecular mechanisms of the pathogenesis, causing the development of multiple tumors in this syndrome, are discussed. The genetic factors promoting a higher incidence of chromosome aberrations simultaneously promote the development of cancer.

Keywords

basal-cell cutaneous carcinoma / Hedgehog and Wnt signaling / genetic syndromes / Gorlin-Goltz syndrome

References

[1] Parren L.J., Frank J. Hereditary tumour syndromes featuring basal cell carcinomas. Br. J. Dermatol. 2011; 165(1): 30-4. doi: 10.1111/j.1365-2133.2011.10334.x.

[2] Гамаюнов С.В., Шумская И.С. Базально-клеточный рак кожи - обзор современного состояния проблемы. Практическая онкология. 2012; 2: 92-106. [Gamayunov S.V., Shumskaya I.S. Basal-cell carcinoma - overview of the current state of the problem. Prakticheskaya onkol-ogiya. 2012; 2: 92-106]. (in Russian)

[3] Снарская Е.С.,. Молочков В.А. Базалиома. М.: Медицина; 2003: 13-26. [Snarskaya E.S, Molochkov V.A. Basal-cell carcinoma (Baza-lioma). Moscow: Meditsina; 2003: 13-26]. (in Russian)

[4] Молочков В.А. Рак кожи при генетических кожных синдромах. Российский журнал кожных и венерических болезней. 2000; 3: 4-14. [Molochkov V.A. Skin cancer in cutaneous genetic syndromes. Rossiyskiy zhurnal kozhnykh i venericheskikh bolezney. 2000; 3: 4-14]. (in Russian)

[5] Заридзе. Д.Г. Канцерогенез. М.: Медицина; 2004: 530-56. [Zaridze D.G. Carcinogenesis (Kantserogenez). Moscow: Meditsina, 2004]. (in Russian)

[6] Беленький Г.Б. Генетические факторы в дерматологии. М.: Медицина; 1970: 124-8. [Belenkiy G.B. Hereditary factors in dermatology (Genetiches-kie faktory v dermatologii). Moscow: Meditsina; 1970: 124-8]. (in Russian)

[7] Xie J., Bartels C.M., Barton S.W., Gu D. Targeting hedgehog signaling in cancer: research and clinical developments. Onco Targets Ther. 2013; 6: 1425-35.

[8] Yang Y Wnt signaling in development and disease. Cell Biosci. 2012; 2(1): 14. doi: 10.1186/2045-3701-2-14.

[9] Rijsewijk F., Schuermann M., Wagenaar E., Parren P., Weigel D., Nusse R. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell. 1987; 50(4): 649-57.

[10] Nusse R., van Ooyen A., Cox D., Fung Y.K., Varmus H. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15. Nature. 1984; 307(5947): 131-6.

[11] Куликова К.В., Кибардин А.В., Гнучев Н.В., Георгиев Г.П., Ларин С.С. Значение сигнального пути Wnt для развития меланомы. Современные технологии в медицине. 2012; 3: 107-12. [Kulikova K.V., Kibardin A.V., Gnuchev N.V., Georgiev G.P., Larin S.S. Meaning of Wnt signaling pathway for the development of melanoma. Sovremennye tekhnologii v meditsine. 2012; 3: 107-12]. (in Russian)

[12] Елькин В.Д., Митрюковский Л.С., Седова Т.Г. Избранная дерматология. Редкие дерматозы и дерматологические синдромы. Пермь; 2004: 546-8. [Elkin V.D., Mitryukovskiy L.S., Sedova T.G. Selected dermatology. Rare deramotoses and dermatological syndromes (Izbran-naya dermatologiya. Redkie dermatozy i dermatologicheskie sindromy). Perm; 2004: 546-8]. (in Russian)

[13] Michaelsson G., Olsson E., Westermark P. The Rombo syndrome: a familial disorder with vermiculate atrophodermia, milia, hypotrichosis, trichoepiteliomas, basal cell carcinomas and peripheral vasodilatation with cyanosis. Acta. Derm. Venerol. 1981; 61(6): 497-503.

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