Genomic screening of testicular germ cell tumors from monozygotic twins

Detalhes bibliográficos
Autor(a) principal: Silveira, Sara Martoreli
Data de Publicação: 2014
Outros Autores: Cunha, Isabela Werneck da, Marchi, Fabio Albuquerque, Busso, Ariane Fidelis, Lopes, Ademar, Rogatto, Silvia Regina [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1186/s13023-014-0181-x
http://hdl.handle.net/11449/117336
Resumo: Background: Testicular germ cell tumors (TGCTs) account for 1-2% of all tumors in young and middle aged men. A 75-fold increase in TCGT development has been reported for monozygotic (MZ) twins. Therefore, the occurrence of simultaneous tumors in MZ twins emphasizes the importance of genetic factors that influence the risk of developing these tumors. Genomic screening was performed for one family containing MZ twins with testicular germ cell tumors, in order to define alterations associated with risk of tumor development.Methods: Copy number alterations were evaluated using array-CGH (4x44K, Agilent Technologies) in one seminoma and one embryonal carcinoma (EC) from MZ twins. In addition, genomic alterations from the tumors and peripheral blood cells of the twins were compared to the parental genomes via their peripheral blood cells.Results: Embryonal carcinoma (Twin-1 t) presented a lower frequency of genomic alterations compared to the seminoma (Twin-2 t). One minimal common region of loss was observed in 9p13.1-p12 in the comparison between DNA from blood samples for Twin-1 and Twin-2. In this region is mapped the CNTNAP3 gene which was confirmed as involved in losses by qPCR. Comparative analysis of novel CNVs between the Twin-1 t and Twin-2 t showed five minimal common regions involving gain at chromosomes 12 (12p12.3-p11.1 and 12p13.33-p12.3), while losses were observed at 10p15.3-p15.2, 13q21.1-q21.2 and 15q11.1-q11.2. In addition, one exclusive rare copy number alteration was detected in Twin-1 t and Twin-2 t, and 19 novel alterations were identified in the Twin-2 t.Conclusion: Distinct genomic profiles for MZ twins with phenotypically different TGCT were described. Of particular interest, 12p gains were detected exclusively in tumor samples. In peripheral blood samples, loss of 9p13.1-p12 was the unique novel CNV shared by the twins, confirming the involvement of CNTNAP3 gene in TGCTs development. Although similar CNV profiles were shared by both the peripheral blood and tumor samples of the twins, tumor-specific CNV loci were identified for seminoma and non-seminomatous tumors. These findings suggest the presence of de novo germline structural alterations and TGCT predisposition.
id UNSP_133f6107a2b57ce31f82d962c73392c3
oai_identifier_str oai:repositorio.unesp.br:11449/117336
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling Genomic screening of testicular germ cell tumors from monozygotic twinsTesticular germ cell tumorsSeminomasEmbryonal carcinomaArray-based comparative genomic hybridizationMolecular markersGenomic imbalancesCopy number variationsBackground: Testicular germ cell tumors (TGCTs) account for 1-2% of all tumors in young and middle aged men. A 75-fold increase in TCGT development has been reported for monozygotic (MZ) twins. Therefore, the occurrence of simultaneous tumors in MZ twins emphasizes the importance of genetic factors that influence the risk of developing these tumors. Genomic screening was performed for one family containing MZ twins with testicular germ cell tumors, in order to define alterations associated with risk of tumor development.Methods: Copy number alterations were evaluated using array-CGH (4x44K, Agilent Technologies) in one seminoma and one embryonal carcinoma (EC) from MZ twins. In addition, genomic alterations from the tumors and peripheral blood cells of the twins were compared to the parental genomes via their peripheral blood cells.Results: Embryonal carcinoma (Twin-1 t) presented a lower frequency of genomic alterations compared to the seminoma (Twin-2 t). One minimal common region of loss was observed in 9p13.1-p12 in the comparison between DNA from blood samples for Twin-1 and Twin-2. In this region is mapped the CNTNAP3 gene which was confirmed as involved in losses by qPCR. Comparative analysis of novel CNVs between the Twin-1 t and Twin-2 t showed five minimal common regions involving gain at chromosomes 12 (12p12.3-p11.1 and 12p13.33-p12.3), while losses were observed at 10p15.3-p15.2, 13q21.1-q21.2 and 15q11.1-q11.2. In addition, one exclusive rare copy number alteration was detected in Twin-1 t and Twin-2 t, and 19 novel alterations were identified in the Twin-2 t.Conclusion: Distinct genomic profiles for MZ twins with phenotypically different TGCT were described. Of particular interest, 12p gains were detected exclusively in tumor samples. In peripheral blood samples, loss of 9p13.1-p12 was the unique novel CNV shared by the twins, confirming the involvement of CNTNAP3 gene in TGCTs development. Although similar CNV profiles were shared by both the peripheral blood and tumor samples of the twins, tumor-specific CNV loci were identified for seminoma and non-seminomatous tumors. These findings suggest the presence of de novo germline structural alterations and TGCT predisposition.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)AC Camargo Canc Ctr, CIPE, Neogene Lab, Sao Paulo, BrazilAC Camargo Canc Ctr, Dept Pathol, Sao Paulo, BrazilUniv Sao Paulo, Inst Math & Stat, Inter Inst Program Bioinformat, BR-09500900 Sao Paulo, BrazilAC Camargo Canc Ctr, Nucl Sarcoma, Dept Pelv Surg, Sao Paulo, BrazilUNESP, Fac Med, Dept Urol, Botucatu, SP, BrazilUNESP, Fac Med, Dept Urol, Botucatu, SP, BrazilBiomed Central LtdAC Camargo Canc CtrUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Silveira, Sara MartoreliCunha, Isabela Werneck daMarchi, Fabio AlbuquerqueBusso, Ariane FidelisLopes, AdemarRogatto, Silvia Regina [UNESP]2015-03-18T15:55:52Z2015-03-18T15:55:52Z2014-11-26info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article9application/pdfhttp://dx.doi.org/10.1186/s13023-014-0181-xOrphanet Journal Of Rare Diseases. London: Biomed Central Ltd, v. 9, 9 p., 2014.1750-1172http://hdl.handle.net/11449/11733610.1186/s13023-014-0181-xWOS:000345665500001WOS000345665500001.pdf2259986546265579Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengOrphanet Journal Of Rare Diseases3.6071,413info:eu-repo/semantics/openAccess2024-09-03T14:30:12Zoai:repositorio.unesp.br:11449/117336Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T14:30:12Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Genomic screening of testicular germ cell tumors from monozygotic twins
title Genomic screening of testicular germ cell tumors from monozygotic twins
spellingShingle Genomic screening of testicular germ cell tumors from monozygotic twins
Silveira, Sara Martoreli
Testicular germ cell tumors
Seminomas
Embryonal carcinoma
Array-based comparative genomic hybridization
Molecular markers
Genomic imbalances
Copy number variations
title_short Genomic screening of testicular germ cell tumors from monozygotic twins
title_full Genomic screening of testicular germ cell tumors from monozygotic twins
title_fullStr Genomic screening of testicular germ cell tumors from monozygotic twins
title_full_unstemmed Genomic screening of testicular germ cell tumors from monozygotic twins
title_sort Genomic screening of testicular germ cell tumors from monozygotic twins
author Silveira, Sara Martoreli
author_facet Silveira, Sara Martoreli
Cunha, Isabela Werneck da
Marchi, Fabio Albuquerque
Busso, Ariane Fidelis
Lopes, Ademar
Rogatto, Silvia Regina [UNESP]
author_role author
author2 Cunha, Isabela Werneck da
Marchi, Fabio Albuquerque
Busso, Ariane Fidelis
Lopes, Ademar
Rogatto, Silvia Regina [UNESP]
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv AC Camargo Canc Ctr
Universidade de São Paulo (USP)
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Silveira, Sara Martoreli
Cunha, Isabela Werneck da
Marchi, Fabio Albuquerque
Busso, Ariane Fidelis
Lopes, Ademar
Rogatto, Silvia Regina [UNESP]
dc.subject.por.fl_str_mv Testicular germ cell tumors
Seminomas
Embryonal carcinoma
Array-based comparative genomic hybridization
Molecular markers
Genomic imbalances
Copy number variations
topic Testicular germ cell tumors
Seminomas
Embryonal carcinoma
Array-based comparative genomic hybridization
Molecular markers
Genomic imbalances
Copy number variations
description Background: Testicular germ cell tumors (TGCTs) account for 1-2% of all tumors in young and middle aged men. A 75-fold increase in TCGT development has been reported for monozygotic (MZ) twins. Therefore, the occurrence of simultaneous tumors in MZ twins emphasizes the importance of genetic factors that influence the risk of developing these tumors. Genomic screening was performed for one family containing MZ twins with testicular germ cell tumors, in order to define alterations associated with risk of tumor development.Methods: Copy number alterations were evaluated using array-CGH (4x44K, Agilent Technologies) in one seminoma and one embryonal carcinoma (EC) from MZ twins. In addition, genomic alterations from the tumors and peripheral blood cells of the twins were compared to the parental genomes via their peripheral blood cells.Results: Embryonal carcinoma (Twin-1 t) presented a lower frequency of genomic alterations compared to the seminoma (Twin-2 t). One minimal common region of loss was observed in 9p13.1-p12 in the comparison between DNA from blood samples for Twin-1 and Twin-2. In this region is mapped the CNTNAP3 gene which was confirmed as involved in losses by qPCR. Comparative analysis of novel CNVs between the Twin-1 t and Twin-2 t showed five minimal common regions involving gain at chromosomes 12 (12p12.3-p11.1 and 12p13.33-p12.3), while losses were observed at 10p15.3-p15.2, 13q21.1-q21.2 and 15q11.1-q11.2. In addition, one exclusive rare copy number alteration was detected in Twin-1 t and Twin-2 t, and 19 novel alterations were identified in the Twin-2 t.Conclusion: Distinct genomic profiles for MZ twins with phenotypically different TGCT were described. Of particular interest, 12p gains were detected exclusively in tumor samples. In peripheral blood samples, loss of 9p13.1-p12 was the unique novel CNV shared by the twins, confirming the involvement of CNTNAP3 gene in TGCTs development. Although similar CNV profiles were shared by both the peripheral blood and tumor samples of the twins, tumor-specific CNV loci were identified for seminoma and non-seminomatous tumors. These findings suggest the presence of de novo germline structural alterations and TGCT predisposition.
publishDate 2014
dc.date.none.fl_str_mv 2014-11-26
2015-03-18T15:55:52Z
2015-03-18T15:55:52Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1186/s13023-014-0181-x
Orphanet Journal Of Rare Diseases. London: Biomed Central Ltd, v. 9, 9 p., 2014.
1750-1172
http://hdl.handle.net/11449/117336
10.1186/s13023-014-0181-x
WOS:000345665500001
WOS000345665500001.pdf
2259986546265579
url http://dx.doi.org/10.1186/s13023-014-0181-x
http://hdl.handle.net/11449/117336
identifier_str_mv Orphanet Journal Of Rare Diseases. London: Biomed Central Ltd, v. 9, 9 p., 2014.
1750-1172
10.1186/s13023-014-0181-x
WOS:000345665500001
WOS000345665500001.pdf
2259986546265579
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Orphanet Journal Of Rare Diseases
3.607
1,413
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9
application/pdf
dc.publisher.none.fl_str_mv Biomed Central Ltd
publisher.none.fl_str_mv Biomed Central Ltd
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
_version_ 1810021411661545472