Assessment of somatic mutations in urine and plasma of Wilms tumor patients
Autor(a) principal: | |
---|---|
Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRN |
Texto Completo: | https://repositorio.ufrn.br/jspui/handle/123456789/29712 |
Resumo: | Tumor DNA has been detected in body fluids of cancer patients. Somatic tumor mutations are being used as biomarkers in body fluids to monitor chemotherapy response as a minimally invasive tool. In this study, we evaluated the potential of tracking somatic mutations in free DNA of plasma and urine collected from Wilms tumor (WT) patients for monitoring treatment response. Wilms tumor is a pediatric renal tumor resulting from cell differentiation errors during nephrogenesis. Its mutational repertoire is not completely defined. Thus, for identifying somatic mutations from tumor tissue DNA, we screened matched tumor/leukocyte DNAs using either a panel containing 16 WT‐associated genes or whole‐exome sequencing (WES). The identified somatic tumor mutations were tracked in urine and plasma DNA collected before, during and after treatment. At least one somatic mutation was identified in five out of six WT tissue samples analyzed. Somatic mutations were detected in body fluids before treatment in all five patients (three patients in urine, three in plasma, and one in both body fluids). In all patients, a decrease of the variant allele fraction of somatic mutations was observed in body fluids during neoadjuvant chemotherapy. Interestingly, the persistence of somatic mutations in body fluids was in accordance with clinical parameters. For one patient who progressed to death, it persisted in high levels in serial body fluid samples during treatment. For three patients without disease progression, somatic mutations were not consistently detected in samples throughout monitoring. For one patient with bilateral disease, a somatic mutation was detected at low levels with no support of clinical manifestation. Our results demonstrated the potential of tracking somatic mutations in urine and plasma DNA as a minimally invasive tool for monitoring WT patients. Additional investigation is needed to check the clinical value of insistent somatic mutations in body fluids. |
id |
UFRN_4a05f7650532a6243f526b6bbca2c0f2 |
---|---|
oai_identifier_str |
oai:https://repositorio.ufrn.br:123456789/29712 |
network_acronym_str |
UFRN |
network_name_str |
Repositório Institucional da UFRN |
repository_id_str |
|
spelling |
Miguez, Ana Carolina KerekesBarros, Bruna D. de FigueiredoSouza, Jorge Estefano Santana deCosta, Cecília Maria L. daCunha, Isabela WerneckBarbosa, Paula Nicole Vieira P.Apezzato, Maria Lúcia P.Souza, Sandro José deCarraro, Dirce Maria2020-07-23T16:24:46Z2020-07-23T16:24:46Z2020-06MIGUEZ, Ana Carolina Kerekes; BARROS, Bruna D. de Figueiredo; SOUZA, Jorge E. S.; COSTA, Cecília Maria L.; CUNHA, Isabela Werneck; BARBOSA, Paula Nicole Vieira P.; APEZZATO, Maria Lúcia P.; SOUZA, Sandro J.; CARRARO, Dirce Maria. Assessment of somatic mutations in urine and plasma of Wilms tumor patients. Cancer Medicine, [S.l.], p. 1-12, jun. 2020. http://dx.doi.org/10.1002/cam4.3236. Disponível em: https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.3236. Acesso em: 23 jul. 2020.https://repositorio.ufrn.br/jspui/handle/123456789/2971210.1002/cam4.3236WileyAttribution 3.0 Brazilhttp://creativecommons.org/licenses/by/3.0/br/info:eu-repo/semantics/openAccessCancer geneticsLiquid biopsyPediatric cancerWilms tumorAssessment of somatic mutations in urine and plasma of Wilms tumor patientsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleTumor DNA has been detected in body fluids of cancer patients. Somatic tumor mutations are being used as biomarkers in body fluids to monitor chemotherapy response as a minimally invasive tool. In this study, we evaluated the potential of tracking somatic mutations in free DNA of plasma and urine collected from Wilms tumor (WT) patients for monitoring treatment response. Wilms tumor is a pediatric renal tumor resulting from cell differentiation errors during nephrogenesis. Its mutational repertoire is not completely defined. Thus, for identifying somatic mutations from tumor tissue DNA, we screened matched tumor/leukocyte DNAs using either a panel containing 16 WT‐associated genes or whole‐exome sequencing (WES). The identified somatic tumor mutations were tracked in urine and plasma DNA collected before, during and after treatment. At least one somatic mutation was identified in five out of six WT tissue samples analyzed. Somatic mutations were detected in body fluids before treatment in all five patients (three patients in urine, three in plasma, and one in both body fluids). In all patients, a decrease of the variant allele fraction of somatic mutations was observed in body fluids during neoadjuvant chemotherapy. Interestingly, the persistence of somatic mutations in body fluids was in accordance with clinical parameters. For one patient who progressed to death, it persisted in high levels in serial body fluid samples during treatment. For three patients without disease progression, somatic mutations were not consistently detected in samples throughout monitoring. For one patient with bilateral disease, a somatic mutation was detected at low levels with no support of clinical manifestation. Our results demonstrated the potential of tracking somatic mutations in urine and plasma DNA as a minimally invasive tool for monitoring WT patients. Additional investigation is needed to check the clinical value of insistent somatic mutations in body fluids.engreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNLICENSElicense.txtlicense.txttext/plain; charset=utf-81484https://repositorio.ufrn.br/bitstream/123456789/29712/3/license.txte9597aa2854d128fd968be5edc8a28d9MD53TEXTAssessmentSomaticMutations_Souza_2020.pdf.txtAssessmentSomaticMutations_Souza_2020.pdf.txtExtracted texttext/plain51282https://repositorio.ufrn.br/bitstream/123456789/29712/4/AssessmentSomaticMutations_Souza_2020.pdf.txt90ceb54c02c35ce3ad074f6bdde03178MD54THUMBNAILAssessmentSomaticMutations_Souza_2020.pdf.jpgAssessmentSomaticMutations_Souza_2020.pdf.jpgGenerated Thumbnailimage/jpeg1795https://repositorio.ufrn.br/bitstream/123456789/29712/5/AssessmentSomaticMutations_Souza_2020.pdf.jpgbbcec8b3fe8e0b4fc042f6f8c28c543cMD55CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8914https://repositorio.ufrn.br/bitstream/123456789/29712/2/license_rdf4d2950bda3d176f570a9f8b328dfbbefMD52123456789/297122022-05-20 17:51:18.682oai:https://repositorio.ufrn.br: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Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2022-05-20T20:51:18Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false |
dc.title.pt_BR.fl_str_mv |
Assessment of somatic mutations in urine and plasma of Wilms tumor patients |
title |
Assessment of somatic mutations in urine and plasma of Wilms tumor patients |
spellingShingle |
Assessment of somatic mutations in urine and plasma of Wilms tumor patients Miguez, Ana Carolina Kerekes Cancer genetics Liquid biopsy Pediatric cancer Wilms tumor |
title_short |
Assessment of somatic mutations in urine and plasma of Wilms tumor patients |
title_full |
Assessment of somatic mutations in urine and plasma of Wilms tumor patients |
title_fullStr |
Assessment of somatic mutations in urine and plasma of Wilms tumor patients |
title_full_unstemmed |
Assessment of somatic mutations in urine and plasma of Wilms tumor patients |
title_sort |
Assessment of somatic mutations in urine and plasma of Wilms tumor patients |
author |
Miguez, Ana Carolina Kerekes |
author_facet |
Miguez, Ana Carolina Kerekes Barros, Bruna D. de Figueiredo Souza, Jorge Estefano Santana de Costa, Cecília Maria L. da Cunha, Isabela Werneck Barbosa, Paula Nicole Vieira P. Apezzato, Maria Lúcia P. Souza, Sandro José de Carraro, Dirce Maria |
author_role |
author |
author2 |
Barros, Bruna D. de Figueiredo Souza, Jorge Estefano Santana de Costa, Cecília Maria L. da Cunha, Isabela Werneck Barbosa, Paula Nicole Vieira P. Apezzato, Maria Lúcia P. Souza, Sandro José de Carraro, Dirce Maria |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Miguez, Ana Carolina Kerekes Barros, Bruna D. de Figueiredo Souza, Jorge Estefano Santana de Costa, Cecília Maria L. da Cunha, Isabela Werneck Barbosa, Paula Nicole Vieira P. Apezzato, Maria Lúcia P. Souza, Sandro José de Carraro, Dirce Maria |
dc.subject.por.fl_str_mv |
Cancer genetics Liquid biopsy Pediatric cancer Wilms tumor |
topic |
Cancer genetics Liquid biopsy Pediatric cancer Wilms tumor |
description |
Tumor DNA has been detected in body fluids of cancer patients. Somatic tumor mutations are being used as biomarkers in body fluids to monitor chemotherapy response as a minimally invasive tool. In this study, we evaluated the potential of tracking somatic mutations in free DNA of plasma and urine collected from Wilms tumor (WT) patients for monitoring treatment response. Wilms tumor is a pediatric renal tumor resulting from cell differentiation errors during nephrogenesis. Its mutational repertoire is not completely defined. Thus, for identifying somatic mutations from tumor tissue DNA, we screened matched tumor/leukocyte DNAs using either a panel containing 16 WT‐associated genes or whole‐exome sequencing (WES). The identified somatic tumor mutations were tracked in urine and plasma DNA collected before, during and after treatment. At least one somatic mutation was identified in five out of six WT tissue samples analyzed. Somatic mutations were detected in body fluids before treatment in all five patients (three patients in urine, three in plasma, and one in both body fluids). In all patients, a decrease of the variant allele fraction of somatic mutations was observed in body fluids during neoadjuvant chemotherapy. Interestingly, the persistence of somatic mutations in body fluids was in accordance with clinical parameters. For one patient who progressed to death, it persisted in high levels in serial body fluid samples during treatment. For three patients without disease progression, somatic mutations were not consistently detected in samples throughout monitoring. For one patient with bilateral disease, a somatic mutation was detected at low levels with no support of clinical manifestation. Our results demonstrated the potential of tracking somatic mutations in urine and plasma DNA as a minimally invasive tool for monitoring WT patients. Additional investigation is needed to check the clinical value of insistent somatic mutations in body fluids. |
publishDate |
2020 |
dc.date.accessioned.fl_str_mv |
2020-07-23T16:24:46Z |
dc.date.available.fl_str_mv |
2020-07-23T16:24:46Z |
dc.date.issued.fl_str_mv |
2020-06 |
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.citation.fl_str_mv |
MIGUEZ, Ana Carolina Kerekes; BARROS, Bruna D. de Figueiredo; SOUZA, Jorge E. S.; COSTA, Cecília Maria L.; CUNHA, Isabela Werneck; BARBOSA, Paula Nicole Vieira P.; APEZZATO, Maria Lúcia P.; SOUZA, Sandro J.; CARRARO, Dirce Maria. Assessment of somatic mutations in urine and plasma of Wilms tumor patients. Cancer Medicine, [S.l.], p. 1-12, jun. 2020. http://dx.doi.org/10.1002/cam4.3236. Disponível em: https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.3236. Acesso em: 23 jul. 2020. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufrn.br/jspui/handle/123456789/29712 |
dc.identifier.doi.none.fl_str_mv |
10.1002/cam4.3236 |
identifier_str_mv |
MIGUEZ, Ana Carolina Kerekes; BARROS, Bruna D. de Figueiredo; SOUZA, Jorge E. S.; COSTA, Cecília Maria L.; CUNHA, Isabela Werneck; BARBOSA, Paula Nicole Vieira P.; APEZZATO, Maria Lúcia P.; SOUZA, Sandro J.; CARRARO, Dirce Maria. Assessment of somatic mutations in urine and plasma of Wilms tumor patients. Cancer Medicine, [S.l.], p. 1-12, jun. 2020. http://dx.doi.org/10.1002/cam4.3236. Disponível em: https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.3236. Acesso em: 23 jul. 2020. 10.1002/cam4.3236 |
url |
https://repositorio.ufrn.br/jspui/handle/123456789/29712 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
Attribution 3.0 Brazil http://creativecommons.org/licenses/by/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution 3.0 Brazil http://creativecommons.org/licenses/by/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Wiley |
publisher.none.fl_str_mv |
Wiley |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFRN instname:Universidade Federal do Rio Grande do Norte (UFRN) instacron:UFRN |
instname_str |
Universidade Federal do Rio Grande do Norte (UFRN) |
instacron_str |
UFRN |
institution |
UFRN |
reponame_str |
Repositório Institucional da UFRN |
collection |
Repositório Institucional da UFRN |
bitstream.url.fl_str_mv |
https://repositorio.ufrn.br/bitstream/123456789/29712/3/license.txt https://repositorio.ufrn.br/bitstream/123456789/29712/4/AssessmentSomaticMutations_Souza_2020.pdf.txt https://repositorio.ufrn.br/bitstream/123456789/29712/5/AssessmentSomaticMutations_Souza_2020.pdf.jpg https://repositorio.ufrn.br/bitstream/123456789/29712/2/license_rdf |
bitstream.checksum.fl_str_mv |
e9597aa2854d128fd968be5edc8a28d9 90ceb54c02c35ce3ad074f6bdde03178 bbcec8b3fe8e0b4fc042f6f8c28c543c 4d2950bda3d176f570a9f8b328dfbbef |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN) |
repository.mail.fl_str_mv |
|
_version_ |
1802117580853346304 |