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

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...

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Autores principales:	Kelly A. Duffy, Kelly D. Getz, Evan R. Hathaway, Mallory E. Byrne, Suzanne P. MacFarland, Jennifer M. Kalish
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Beckwith–Wiedemann Syndrome Beckwith–Wiedemann Spectrum cancer predisposition tumor screening hepatoblastoma genotype-phenotype Genetics QH426-470
Acceso en línea:	https://doaj.org/article/aac4e3b81bc14a7a8d07535b0226bee8
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spelling	oai:doaj.org-article:aac4e3b81bc14a7a8d07535b0226bee82021-11-25T17:42:35ZCharacteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith–Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population10.3390/genes121118392073-4425https://doaj.org/article/aac4e3b81bc14a7a8d07535b0226bee82021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1839https://doaj.org/toc/2073-4425Beckwith–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.Kelly A. DuffyKelly D. GetzEvan R. HathawayMallory E. ByrneSuzanne P. MacFarlandJennifer M. KalishMDPI AGarticleBeckwith–Wiedemann SyndromeBeckwith–Wiedemann Spectrumcancer predispositiontumor screeninghepatoblastomagenotype-phenotypeGeneticsQH426-470ENGenes, Vol 12, Iss 1839, p 1839 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Beckwith–Wiedemann Syndrome Beckwith–Wiedemann Spectrum cancer predisposition tumor screening hepatoblastoma genotype-phenotype Genetics QH426-470
spellingShingle	Beckwith–Wiedemann Syndrome Beckwith–Wiedemann Spectrum cancer predisposition tumor screening hepatoblastoma genotype-phenotype Genetics QH426-470 Kelly A. Duffy Kelly D. Getz Evan R. Hathaway Mallory E. Byrne Suzanne P. MacFarland Jennifer M. Kalish Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith–Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population
description	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.
format	article
author	Kelly A. Duffy Kelly D. Getz Evan R. Hathaway Mallory E. Byrne Suzanne P. MacFarland Jennifer M. Kalish
author_facet	Kelly A. Duffy Kelly D. Getz Evan R. Hathaway Mallory E. Byrne Suzanne P. MacFarland Jennifer M. Kalish
author_sort	Kelly A. Duffy
title	Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith–Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population
title_short	Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith–Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population
title_full	Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith–Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population
title_fullStr	Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith–Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population
title_full_unstemmed	Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith–Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population
title_sort	characteristics associated with tumor development in individuals diagnosed with beckwith–wiedemann spectrum: novel tumor-(epi)genotype-phenotype associations in the bwsp population
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/aac4e3b81bc14a7a8d07535b0226bee8
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Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith–Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population

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