The role of retroelements in the development of hereditary tumor syndromes

Abstract

Genomic instability caused by activated retroelements plays an important role in the development of malignant neoplasms. Activated retroelements cause enhanced expression of oncogenes containing transposon sequences in their promoters and introns. Oncosuppressor genes contain hot spots of insertional mutagenesis, therefore retroelements cause their inactivation. As a result, genomic instability increases during the development of tumors, since oncosuppressors normally silence retrotransposons. Accordingly, inactivation of the oncosuppressor causes increased expression of retroelements.The study objective is to describe the role of retrotransposons on the development of hereditary tumor syndromes, which will allow a new look at the classical concepts of carcinogenesis. The data we have described allow us to consider in a new way the Knudson’s two-hit hypothesis in hereditary tumor syndromes, since the germinal inactivation of 1 allele of the oncosuppressor gene promotes the development of malignant tumors due to an increase in the activity of transposons. The consequence of the developed instability in the tumor is the inactivation of the second allele of the oncosuppressor gene, which contributes to clonal evolution and the progression of carcinogenesis.

Keywords

• carcinogenesis
• hereditary tumor syndromes
• oncogenes
• tumor suppressors
• retroelements