Monozygotic twins with neuroblastoma MS have a similar molecular profile: a case of twin-to-twin metastasis

Abstract

Fetoplacental neuroblastoma metastasis has been postulated as a mechanism accounting for concordant cases where one twin develops a primary tumour and the second twin manifests the disease without an identifiable primary site. These tumours may originate and spread concomitantly due to the same genetic background shared by monozygotic twins. This study investigated the molecular profile of stage MS neuroblastoma presenting concomitantly in monozygotic twins. Comparative genomic hybridisation (aCGH) was done for each of the twin liver tumour and peripheral blood samples at diagnosis. Comparison of copy-number variation (CNV) regions revealed a set of CNVs that were common to both tumour specimens and not apparent in the blood. The CNV signature in both twins’ tumours was highly similar, suggesting a common clonal origin. Additional findings included large deletion of chromosome 10 and amplification of chromosome 17. Notably, both liver samples had amplification of a short region involving DEIN (chromosome 4q34.1). Similar CNVs strongly support a common clonal origin and metastatic spread from one twin to the other. DEIN is a long-coding RNA (IncRNA) that has been found highly expressed in stage MS neuroblastoma and is likely involved in biological processes such as cell migration and metastasis.

Clinical, Histological, Cytogenetic and Molecular Analysis of Monozygous Twins with Wilms Tumor

“…Although the accurate reason for the origins of the same tumors at a similar time in multiples is not well known yet, there are two hypotheses explaining that phenomenon. The first theory suggests that tumors in twins arise from transplacental spread [ 20 , 21 ]. In a publication by Shatar et al, such a mechanism was suggested in a case of twins with neuroblastoma, where one twin developed a primary tumor, and the other had metastatic disease without a clear primary location.…”

“…The signature of copy number changes in the tumors of both twins was similar and suggested a common clonal origin. Additional findings included large deletion of chromosome 10 and amplification of chromosome 17 [ 20 ].…”