Genomic screening of testicular germ cell tumors from monozygotic twins
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , |
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. |
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Repositório Institucional da UNESP |
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2946 |
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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 |