Supervisors info:
Ιωάννα Traeger – Συνοδινού, Καθηγήτρια, Ιατρική Σχολή, Ε.Κ.Π.Α., Επιβλέπουσα
Μαρία Τζέτη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, Ε.Κ.Π.Α.
Κυριακή Κέκου, Ε.Δ.Ι.Π., Ιατρική Σχολή, Ε.Κ.Π.Α.
Summary:
TITLE: Digenic inheritance as a predisposing factor in childhood cancer
INTRODUCTION: Cancer is a genetic disease resulting from many alterations/mutations in the DNA sequence that deregulates normal cellular activity. It is the second most common cause of death in children aged 1 to 14 years, with its incidence rate increasing by 0.7%, annually since 1975. One of its major causes is the presence of inherited mutations in cancer predisposition genes (CPGs), which is associated with the development of cancer predisposition syndromes (CPSs). Recently, through the advancement of molecular genetics, it has been suggested that childhood cancer may also be predisposed to combinations of variants in two different and co-operating cancer predisposition genes (CPGs) of the same pathway, a phenomenon called digenic inheritance.
AIM OF STUDY: The purpose of this study is to identify, present, describe and investigate cases of digenic inheritance that predispose childhood cancer.
METHODS: A literature review of related to theme publications was performed using biological and biomedical search engines and databases, most notably PubMed and Google Scholar. In the case of individual articles and papers, the main method used was trio-WES.
RESULTS: Significant predisposing effects of cancer were found in children and a teenage girl, due to digenic inheritance. In particular, it was found that digenic inheritance of germline mutations in the EPCAM-MSH2, PTCH1-PTCH2, BRIP1-HIPK2, APC-MSH2, and TP53-ERCC3 genes, respectively, caused colorectal cancer in an 9-year-old girl, fetal rhabdomyosarcoma, osteosarcoma in an 11-year-old girl, colorectal cancer in a 16-year-old adolescent, and adrenal carcinoma (LFS tumor) in a 4-year-old boy.
CONCLUSIONS: Although pediatric cancer is a growing subject of research, data regarding its digenic inheritance are limited. However, the literature to date confirms the ability of digenic inherited mutations/pathogenic variants in cancer predisposition genes (CPGs), which share common pathways, to predispose to cancer in childhood and adolescence. Similar data have been found in cases of adult cancers, such as hereditary colorectal cancer (MUTYH, OGG1) and breast and ovarian cancer (BRCA1, BRCA2). Therefore, further investigation of digenic inherited cancers is needed.
Keywords:
Digenic inheritance, Child cancer, Digenic mutations, Cancer prediction syndromes, Cancer prediction genes
