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High-Resolution Array CGH Profiling Identifies Na/K Transporting ATPase Interacting 2 (NKAIN2) as a Predisposing Candidate Gene in Neuroblastoma

Neuroblastoma (NB), the most common solid cancer in early childhood, usually occurs sporadically but also its familial occurance is known in 1-2% of NB patients. Germline mutations in the ALK and PHOX2B genes have been found in a subset of familial NBs. However, because some individuals harbouring m...

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Autores principales: Romania, Paolo, Castellano, Aurora, Surace, Cecilia, Citti, Arianna, De Ioris, Maria Antonietta, Sirleto, Pietro, De Mariano, Marilena, Longo, Luca, Boldrini, Renata, Angioni, Adriano, Locatelli, Franco, Fruci, Doriana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808344/
https://www.ncbi.nlm.nih.gov/pubmed/24205241
http://dx.doi.org/10.1371/journal.pone.0078481
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author Romania, Paolo
Castellano, Aurora
Surace, Cecilia
Citti, Arianna
De Ioris, Maria Antonietta
Sirleto, Pietro
De Mariano, Marilena
Longo, Luca
Boldrini, Renata
Angioni, Adriano
Locatelli, Franco
Fruci, Doriana
author_facet Romania, Paolo
Castellano, Aurora
Surace, Cecilia
Citti, Arianna
De Ioris, Maria Antonietta
Sirleto, Pietro
De Mariano, Marilena
Longo, Luca
Boldrini, Renata
Angioni, Adriano
Locatelli, Franco
Fruci, Doriana
author_sort Romania, Paolo
collection PubMed
description Neuroblastoma (NB), the most common solid cancer in early childhood, usually occurs sporadically but also its familial occurance is known in 1-2% of NB patients. Germline mutations in the ALK and PHOX2B genes have been found in a subset of familial NBs. However, because some individuals harbouring mutations in these genes do not develop this tumor, additional genetic alterations appear to be required for NB pathogenesis. Herein, we studied an Italian family with three NB patients, two siblings and a first cousin, carrying an ALK germline-activating mutation R1192P, that was inherited from their unaffected mothers and with no mutations in the PHOX2B gene. A comparison between somatic and germline DNA copy number changes in the two affected siblings by a high resolution array-based Comparative Genomic Hybridization (CGH) analysis revealed a germline gain at NKAIN2 (Na/K transporting ATPase interacting 2) locus in one of the sibling, that was inherited from the parent who does not carry the ALK mutation. Surprisingly, NKAIN2 was expressed at high levels also in the affected sibling that lacks the genomic gain at this locus, clearly suggesting the existance of other regulatory mechanisms. High levels of NKAIN2 were detected in the MYCN-amplified NB cell lines and in the most aggressive NB lesions as well as in the peripheral blood of a large cohort of NB patients. Consistent with a role of NKAIN2 in NB development, NKAIN2 was down-regulated during all-trans retinoic acid differentiation in two NB cell lines. Taken together, these data indicate a potential role of NKAIN2 gene in NB growth and differentiation.
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spelling pubmed-38083442013-11-07 High-Resolution Array CGH Profiling Identifies Na/K Transporting ATPase Interacting 2 (NKAIN2) as a Predisposing Candidate Gene in Neuroblastoma Romania, Paolo Castellano, Aurora Surace, Cecilia Citti, Arianna De Ioris, Maria Antonietta Sirleto, Pietro De Mariano, Marilena Longo, Luca Boldrini, Renata Angioni, Adriano Locatelli, Franco Fruci, Doriana PLoS One Research Article Neuroblastoma (NB), the most common solid cancer in early childhood, usually occurs sporadically but also its familial occurance is known in 1-2% of NB patients. Germline mutations in the ALK and PHOX2B genes have been found in a subset of familial NBs. However, because some individuals harbouring mutations in these genes do not develop this tumor, additional genetic alterations appear to be required for NB pathogenesis. Herein, we studied an Italian family with three NB patients, two siblings and a first cousin, carrying an ALK germline-activating mutation R1192P, that was inherited from their unaffected mothers and with no mutations in the PHOX2B gene. A comparison between somatic and germline DNA copy number changes in the two affected siblings by a high resolution array-based Comparative Genomic Hybridization (CGH) analysis revealed a germline gain at NKAIN2 (Na/K transporting ATPase interacting 2) locus in one of the sibling, that was inherited from the parent who does not carry the ALK mutation. Surprisingly, NKAIN2 was expressed at high levels also in the affected sibling that lacks the genomic gain at this locus, clearly suggesting the existance of other regulatory mechanisms. High levels of NKAIN2 were detected in the MYCN-amplified NB cell lines and in the most aggressive NB lesions as well as in the peripheral blood of a large cohort of NB patients. Consistent with a role of NKAIN2 in NB development, NKAIN2 was down-regulated during all-trans retinoic acid differentiation in two NB cell lines. Taken together, these data indicate a potential role of NKAIN2 gene in NB growth and differentiation. Public Library of Science 2013-10-25 /pmc/articles/PMC3808344/ /pubmed/24205241 http://dx.doi.org/10.1371/journal.pone.0078481 Text en © 2013 Romania et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Romania, Paolo
Castellano, Aurora
Surace, Cecilia
Citti, Arianna
De Ioris, Maria Antonietta
Sirleto, Pietro
De Mariano, Marilena
Longo, Luca
Boldrini, Renata
Angioni, Adriano
Locatelli, Franco
Fruci, Doriana
High-Resolution Array CGH Profiling Identifies Na/K Transporting ATPase Interacting 2 (NKAIN2) as a Predisposing Candidate Gene in Neuroblastoma
title High-Resolution Array CGH Profiling Identifies Na/K Transporting ATPase Interacting 2 (NKAIN2) as a Predisposing Candidate Gene in Neuroblastoma
title_full High-Resolution Array CGH Profiling Identifies Na/K Transporting ATPase Interacting 2 (NKAIN2) as a Predisposing Candidate Gene in Neuroblastoma
title_fullStr High-Resolution Array CGH Profiling Identifies Na/K Transporting ATPase Interacting 2 (NKAIN2) as a Predisposing Candidate Gene in Neuroblastoma
title_full_unstemmed High-Resolution Array CGH Profiling Identifies Na/K Transporting ATPase Interacting 2 (NKAIN2) as a Predisposing Candidate Gene in Neuroblastoma
title_short High-Resolution Array CGH Profiling Identifies Na/K Transporting ATPase Interacting 2 (NKAIN2) as a Predisposing Candidate Gene in Neuroblastoma
title_sort high-resolution array cgh profiling identifies na/k transporting atpase interacting 2 (nkain2) as a predisposing candidate gene in neuroblastoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808344/
https://www.ncbi.nlm.nih.gov/pubmed/24205241
http://dx.doi.org/10.1371/journal.pone.0078481
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