Expression of BARD1 β Isoform in Selected Pediatric Tumors.

Anna Jasiak,Grzegorz Cichosz,Natalia Krawczyńska,Joanna Stefanowicz,Ewa Iżycka-Świeszewska,Mariola Iliszko,Katarzyna Czarnota,Elżbieta Adamkiewicz-Drożyńska,Kamil Buczkowski

doi:10.3390/genes12020168

Abstract

Currently, many new possible biomarkers and mechanisms are being searched and tested to analyse pathobiology of pediatric tumours for the development of new treatments. One such candidate molecular factor is BARD1 (BRCA1 Associated RING Domain 1)—a tumour-suppressing gene involved in cell cycle control and genome stability, engaged in several types of adult-type tumours. The data on BARD1 significance in childhood cancer is limited. This study determines the expression level of BARD1 and its isoform beta (β) in three different histogenetic groups of pediatric cancer—neuroblastic tumours, and for the first time in chosen germ cell tumours (GCT), and rhabdomyosarcoma (RMS), using the qPCR method. We found higher expression of beta isoform in tumour compared to healthy tissue with no such changes concerning BARD1 full-length. Additionally, differences in expression of BARD1 β between histological types of neuroblastic tumours were observed, with higher levels in ganglioneuroblastoma and ganglioneuroma. Furthermore, a higher expression of BARD1 β characterized yolk sac tumours (GCT type) and RMS when comparing with non-neoplastic tissue. These tumours also showed a high expression of the TERT (Telomerase Reverse Transcriptase) gene. In two RMS cases we found deep decrease of BARD1 β in post-chemotherapy samples. This work supports the oncogenicity of the beta isoform in pediatric tumours, as well as demonstrates the differences in its expression depending on the histological type of neoplasm, and the level of maturation in neuroblastic tumours.

Highlights

IntroductionSignificant patho-clinical heterogeneity of pediatric tumours, together with their low incidence, results in the limited number of ongoing studies, compared to the adult malignancies
In the results of BARD1 Full length (FL) expression and the beta isoform for the whole material from neoplastic tissue (n = 120; FL: 0.0111 ± 0.0123; β: 0.004 ± 0.0048) and healthy tissue (n = 26; FL: 0.0063 ± 0.0048; β: 0.002 ± 0.0025), we found that there were no statistically significant differences in the level of FL expression
When analyzing BARD1 β compared to FL expression depending on germ cell tumours (GCT) subtype, we found a higher correlation in yolk sac tumour (YCT) tissue (0.617 ± 0.151) than adjacent healthy tissues (0.243 ± 0.0729) (Z = 2.07; p = 0.02)

Summary

Introduction

Significant patho-clinical heterogeneity of pediatric tumours, together with their low incidence, results in the limited number of ongoing studies, compared to the adult malignancies. The pathogenesis of pediatric cancers’ differs significantly from adulthood tumours, with a little importance of environmental factors [1]. Cancer is the second cause of death in children, and the reason for morbidity is that most survivors suffer from various long-term side post-treatment effects. Pediatric cancer occurs in the context of development and developmental biology.

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