Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith-Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population.

TitleCharacteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith-Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population.
Publication TypeJournal Article
Year of Publication2021
AuthorsDuffy KA, Getz KD, Hathaway ER, Byrne ME, MacFarland SP, Kalish JM
JournalGenes (Basel)
Volume12
Issue11
Date Published2021 11 21
ISSN2073-4425
KeywordsAdult, Aged, Beckwith-Wiedemann Syndrome, Epigenesis, Genetic, Female, Genotype, Humans, Male, Middle Aged, Phenotype, Tumor Burden
Abstract

Beckwith-Wiedemann Spectrum (BWSp) is the most common epigenetic childhood cancer predisposition disorder. BWSp is caused by (epi)genetic changes affecting the BWS critical region on chromosome 11p15. Clinically, BWSp represents complex molecular and phenotypic heterogeneity resulting in a range of presentations from Classic BWS to milder features. The previously reported tumor risk based on Classic BWS cohorts is 8-10% and routine tumor screening has been recommended. This work investigated the tumor risk and correlation with phenotype within a cohort of patients from Classic BWS to BWSp using a mixed-methods approach to explore phenotype and epigenotype profiles associated with tumor development through statistical analyses with post-hoc retrospective case series review. We demonstrated that tumor risk across BWSp differs from Classic BWS and that certain phenotypic features are associated with specific epigenetic causes; nephromegaly and/or hyperinsulinism appear associated with cancer in some patients. We also demonstrated that prenatal and perinatal factors that are not currently part of the BWSp classification may factor into tumor risk. Additionally, blood testing results are not necessarily synonymous with tissue testing results. Together, it appears that the current understanding from Classic BWS of (epi)genetics and phenotype correlations with tumors is not represented in the BWSp. Further study is needed in this complex population.

DOI10.3390/genes12111839
Alternate JournalGenes (Basel)
PubMed ID34828445
PubMed Central IDPMC8621885
Grant ListK08 CA193915 / NH / NIH HHS / United States