Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment

Pediatric adrenocortical tumors (ACTs) are rare and heterogeneous. Approximately 50% of children with ACT carry a germline TP53 variant; however, the genetic underpinning of remaining cases has not been elucidated. In patients having germline TP53 variants, loss of maternal chromosome 11 and duplica...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Emilia Modolo Pinto, Carlos Rodriguez-Galindo, Catherine G. Lam, Robert E. Ruiz, Gerard P. Zambetti, Raul C. Ribeiro
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Beckwith-Wiedemann syndrome adrenocortical cancer hemihypertrophia chromosome 11p15 TP53 UPD Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/b185a85e41364ff1b358316a95e9282a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b185a85e41364ff1b358316a95e9282a
record_format	dspace
spelling	oai:doaj.org-article:b185a85e41364ff1b358316a95e9282a2021-11-05T14:52:02ZAdrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment1664-239210.3389/fendo.2021.756523https://doaj.org/article/b185a85e41364ff1b358316a95e9282a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.756523/fullhttps://doaj.org/toc/1664-2392Pediatric adrenocortical tumors (ACTs) are rare and heterogeneous. Approximately 50% of children with ACT carry a germline TP53 variant; however, the genetic underpinning of remaining cases has not been elucidated. In patients having germline TP53 variants, loss of maternal chromosome 11 and duplication of the paternal copy [paternal uniparental disomy, (UPD)] occurs early in tumorigenesis and explains the overexpression of IGF2, the hallmark of pediatric ACT. Beckwith-Wiedemann syndrome (BWS) is also associated with overexpression of IGF2 due to disruption of the 11p15 loci, including segmental UPD. Here, we report six children with ACT with wild type TP53 and germline paternal 11p15 UPD. Median age of five girls and one boy was 3.2 years (range 0.5-11 years). Two patients met the criteria for BWS before diagnosis of ACT. However, ACT was the first and only manifestation of paternal 11p15 UPD in four children. Tumor weight ranged from 21.5 g to 550 g. Despite poor prognostic features at presentation, such as pulmonary metastasis, bilateral adrenal involvement, and large tumors, all patients are alive 8-21 years after cancer diagnosis. Our observations suggest that children with ACT and wild type TP53, irrespective of their age, should be screened for germline abnormalities in chromosome 11p15.Emilia Modolo PintoCarlos Rodriguez-GalindoCarlos Rodriguez-GalindoCatherine G. LamCatherine G. LamRobert E. RuizGerard P. ZambettiRaul C. RibeiroFrontiers Media S.A.articleBeckwith-Wiedemann syndromeadrenocortical cancerhemihypertrophiachromosome 11p15TP53UPDDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Beckwith-Wiedemann syndrome adrenocortical cancer hemihypertrophia chromosome 11p15 TP53 UPD Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	Beckwith-Wiedemann syndrome adrenocortical cancer hemihypertrophia chromosome 11p15 TP53 UPD Diseases of the endocrine glands. Clinical endocrinology RC648-665 Emilia Modolo Pinto Carlos Rodriguez-Galindo Carlos Rodriguez-Galindo Catherine G. Lam Catherine G. Lam Robert E. Ruiz Gerard P. Zambetti Raul C. Ribeiro Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment
description	Pediatric adrenocortical tumors (ACTs) are rare and heterogeneous. Approximately 50% of children with ACT carry a germline TP53 variant; however, the genetic underpinning of remaining cases has not been elucidated. In patients having germline TP53 variants, loss of maternal chromosome 11 and duplication of the paternal copy [paternal uniparental disomy, (UPD)] occurs early in tumorigenesis and explains the overexpression of IGF2, the hallmark of pediatric ACT. Beckwith-Wiedemann syndrome (BWS) is also associated with overexpression of IGF2 due to disruption of the 11p15 loci, including segmental UPD. Here, we report six children with ACT with wild type TP53 and germline paternal 11p15 UPD. Median age of five girls and one boy was 3.2 years (range 0.5-11 years). Two patients met the criteria for BWS before diagnosis of ACT. However, ACT was the first and only manifestation of paternal 11p15 UPD in four children. Tumor weight ranged from 21.5 g to 550 g. Despite poor prognostic features at presentation, such as pulmonary metastasis, bilateral adrenal involvement, and large tumors, all patients are alive 8-21 years after cancer diagnosis. Our observations suggest that children with ACT and wild type TP53, irrespective of their age, should be screened for germline abnormalities in chromosome 11p15.
format	article
author	Emilia Modolo Pinto Carlos Rodriguez-Galindo Carlos Rodriguez-Galindo Catherine G. Lam Catherine G. Lam Robert E. Ruiz Gerard P. Zambetti Raul C. Ribeiro
author_facet	Emilia Modolo Pinto Carlos Rodriguez-Galindo Carlos Rodriguez-Galindo Catherine G. Lam Catherine G. Lam Robert E. Ruiz Gerard P. Zambetti Raul C. Ribeiro
author_sort	Emilia Modolo Pinto
title	Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment
title_short	Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment
title_full	Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment
title_fullStr	Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment
title_full_unstemmed	Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment
title_sort	adrenocortical tumors in children with constitutive chromosome 11p15 paternal uniparental disomy: implications for diagnosis and treatment
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b185a85e41364ff1b358316a95e9282a
work_keys_str_mv	AT emiliamodolopinto adrenocorticaltumorsinchildrenwithconstitutivechromosome11p15paternaluniparentaldisomyimplicationsfordiagnosisandtreatment AT carlosrodriguezgalindo adrenocorticaltumorsinchildrenwithconstitutivechromosome11p15paternaluniparentaldisomyimplicationsfordiagnosisandtreatment AT carlosrodriguezgalindo adrenocorticaltumorsinchildrenwithconstitutivechromosome11p15paternaluniparentaldisomyimplicationsfordiagnosisandtreatment AT catherineglam adrenocorticaltumorsinchildrenwithconstitutivechromosome11p15paternaluniparentaldisomyimplicationsfordiagnosisandtreatment AT catherineglam adrenocorticaltumorsinchildrenwithconstitutivechromosome11p15paternaluniparentaldisomyimplicationsfordiagnosisandtreatment AT roberteruiz adrenocorticaltumorsinchildrenwithconstitutivechromosome11p15paternaluniparentaldisomyimplicationsfordiagnosisandtreatment AT gerardpzambetti adrenocorticaltumorsinchildrenwithconstitutivechromosome11p15paternaluniparentaldisomyimplicationsfordiagnosisandtreatment AT raulcribeiro adrenocorticaltumorsinchildrenwithconstitutivechromosome11p15paternaluniparentaldisomyimplicationsfordiagnosisandtreatment
_version_	1718444250502266880

Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment

Ejemplares similares