Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRN |
Texto Completo: | https://repositorio.ufrn.br/jspui/handle/123456789/25924 |
Resumo: | Background: The observation of tumor-derived cell-free DNA (ctDNA) in plasma brought new expectations to monitor treatment response in cancer patients. Case presentation: In an exploratory case of a 57-year-old man diagnosed with metastatic sigmoid adenocarcinoma, we used a hotspot panel of cancer-associated gene mutations to identify tumor-specific mutations in the primary tumor and metastasis. Results: Five mutations were detected (KRAS, p.Gly12Val; TP53, p.Arg175His; RB1, p.Ile680Thr; ALK, p.Gly1184Glu; and ERBB2, p.Lys860Lys), of which three were detected in both tissue types (primary tumor and metastasis). All five mutations were monitored in the ctDNA of six serial plasma samples. Only KRAS and TP53 mutations were detected at a high frequency in the first plasma sample. After 1 month of chemotherapy the allele frequencies of both mutations fell below the detection limit. From the third month of systemic treatment onward, the allele frequencies of both mutations were detectable in plasma, displaying a continual increase thereafter. The remaining three mutations were not detected in plasma samples. Signs of disease progression in ctDNA during the treatment period were evident while computed tomography (CT) measurements suggested stable metastatic lesions throughout the treatment. Conclusions: Liquid biopsies revealed tumor heterogeneity and predicted tumor progression, demonstrating the potential of ctDNA analysis to be a sensitive and specific tool for monitoring treatment responsivity and for early identification of treatment resistance. |
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Barros, Bruna D. de FigueiredoKupper, Bruna E. C.Aguiar Junior, SamuelMello, Celso A. L. deBegnam, Maria D.Chojniak, RubensSouza, Sandro José deTorrezan, Giovana T.Carraro, Dirce M.2018-10-02T14:29:55Z2018-10-02T14:29:55Z2018-08-10BARROS, B. D. F. et al. Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer. Front. Oncol., v. 8, p. 306, ago/2018.https://repositorio.ufrn.br/jspui/handle/123456789/2592410.3389/fonc.2018.00306engliquid biopsyctDNAcolorectal cancerNGSgene panelMutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancerinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleBackground: The observation of tumor-derived cell-free DNA (ctDNA) in plasma brought new expectations to monitor treatment response in cancer patients. Case presentation: In an exploratory case of a 57-year-old man diagnosed with metastatic sigmoid adenocarcinoma, we used a hotspot panel of cancer-associated gene mutations to identify tumor-specific mutations in the primary tumor and metastasis. Results: Five mutations were detected (KRAS, p.Gly12Val; TP53, p.Arg175His; RB1, p.Ile680Thr; ALK, p.Gly1184Glu; and ERBB2, p.Lys860Lys), of which three were detected in both tissue types (primary tumor and metastasis). All five mutations were monitored in the ctDNA of six serial plasma samples. Only KRAS and TP53 mutations were detected at a high frequency in the first plasma sample. After 1 month of chemotherapy the allele frequencies of both mutations fell below the detection limit. From the third month of systemic treatment onward, the allele frequencies of both mutations were detectable in plasma, displaying a continual increase thereafter. The remaining three mutations were not detected in plasma samples. Signs of disease progression in ctDNA during the treatment period were evident while computed tomography (CT) measurements suggested stable metastatic lesions throughout the treatment. Conclusions: Liquid biopsies revealed tumor heterogeneity and predicted tumor progression, demonstrating the potential of ctDNA analysis to be a sensitive and specific tool for monitoring treatment responsivity and for early identification of treatment resistance.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNORIGINALSandroSouza_ICe_2018_Mutation detection.pdfSandroSouza_ICe_2018_Mutation detection.pdfSandroSouza_ICe_2018_Mutation detectionapplication/pdf573402https://repositorio.ufrn.br/bitstream/123456789/25924/1/SandroSouza_ICe_2018_Mutation%20detection.pdf5f76b7315909fd419c3da51e43a42185MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.ufrn.br/bitstream/123456789/25924/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52TEXTSandroSouza_ICe_2018_Mutation detection.pdf.txtSandroSouza_ICe_2018_Mutation detection.pdf.txtExtracted texttext/plain29946https://repositorio.ufrn.br/bitstream/123456789/25924/3/SandroSouza_ICe_2018_Mutation%20detection.pdf.txtdf03add9f1cd0d451588af6b963bb2b7MD53THUMBNAILSandroSouza_ICe_2018_Mutation detection.pdf.jpgSandroSouza_ICe_2018_Mutation detection.pdf.jpgIM Thumbnailimage/jpeg10683https://repositorio.ufrn.br/bitstream/123456789/25924/4/SandroSouza_ICe_2018_Mutation%20detection.pdf.jpgcd3baff7a2c5025664b47d6c38bb558dMD54123456789/259242021-07-09 19:45:07.666oai:https://repositorio.ufrn.br:123456789/25924Tk9URTogUExBQ0UgWU9VUiBPV04gTElDRU5TRSBIRVJFClRoaXMgc2FtcGxlIGxpY2Vuc2UgaXMgcHJvdmlkZWQgZm9yIGluZm9ybWF0aW9uYWwgcHVycG9zZXMgb25seS4KCk5PTi1FWENMVVNJVkUgRElTVFJJQlVUSU9OIExJQ0VOU0UKCkJ5IHNpZ25pbmcgYW5kIHN1Ym1pdHRpbmcgdGhpcyBsaWNlbnNlLCB5b3UgKHRoZSBhdXRob3Iocykgb3IgY29weXJpZ2h0Cm93bmVyKSBncmFudHMgdG8gRFNwYWNlIFVuaXZlcnNpdHkgKERTVSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBEU1UgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgRFNVIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgRFNVIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gRFNVLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpEU1Ugd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2021-07-09T22:45:07Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false |
dc.title.pt_BR.fl_str_mv |
Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer |
title |
Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer |
spellingShingle |
Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer Barros, Bruna D. de Figueiredo liquid biopsy ctDNA colorectal cancer NGS gene panel |
title_short |
Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer |
title_full |
Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer |
title_fullStr |
Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer |
title_full_unstemmed |
Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer |
title_sort |
Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer |
author |
Barros, Bruna D. de Figueiredo |
author_facet |
Barros, Bruna D. de Figueiredo Kupper, Bruna E. C. Aguiar Junior, Samuel Mello, Celso A. L. de Begnam, Maria D. Chojniak, Rubens Souza, Sandro José de Torrezan, Giovana T. Carraro, Dirce M. |
author_role |
author |
author2 |
Kupper, Bruna E. C. Aguiar Junior, Samuel Mello, Celso A. L. de Begnam, Maria D. Chojniak, Rubens Souza, Sandro José de Torrezan, Giovana T. Carraro, Dirce M. |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Barros, Bruna D. de Figueiredo Kupper, Bruna E. C. Aguiar Junior, Samuel Mello, Celso A. L. de Begnam, Maria D. Chojniak, Rubens Souza, Sandro José de Torrezan, Giovana T. Carraro, Dirce M. |
dc.subject.por.fl_str_mv |
liquid biopsy ctDNA colorectal cancer NGS gene panel |
topic |
liquid biopsy ctDNA colorectal cancer NGS gene panel |
description |
Background: The observation of tumor-derived cell-free DNA (ctDNA) in plasma brought new expectations to monitor treatment response in cancer patients. Case presentation: In an exploratory case of a 57-year-old man diagnosed with metastatic sigmoid adenocarcinoma, we used a hotspot panel of cancer-associated gene mutations to identify tumor-specific mutations in the primary tumor and metastasis. Results: Five mutations were detected (KRAS, p.Gly12Val; TP53, p.Arg175His; RB1, p.Ile680Thr; ALK, p.Gly1184Glu; and ERBB2, p.Lys860Lys), of which three were detected in both tissue types (primary tumor and metastasis). All five mutations were monitored in the ctDNA of six serial plasma samples. Only KRAS and TP53 mutations were detected at a high frequency in the first plasma sample. After 1 month of chemotherapy the allele frequencies of both mutations fell below the detection limit. From the third month of systemic treatment onward, the allele frequencies of both mutations were detectable in plasma, displaying a continual increase thereafter. The remaining three mutations were not detected in plasma samples. Signs of disease progression in ctDNA during the treatment period were evident while computed tomography (CT) measurements suggested stable metastatic lesions throughout the treatment. Conclusions: Liquid biopsies revealed tumor heterogeneity and predicted tumor progression, demonstrating the potential of ctDNA analysis to be a sensitive and specific tool for monitoring treatment responsivity and for early identification of treatment resistance. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-10-02T14:29:55Z |
dc.date.available.fl_str_mv |
2018-10-02T14:29:55Z |
dc.date.issued.fl_str_mv |
2018-08-10 |
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 |
BARROS, B. D. F. et al. Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer. Front. Oncol., v. 8, p. 306, ago/2018. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufrn.br/jspui/handle/123456789/25924 |
dc.identifier.doi.none.fl_str_mv |
10.3389/fonc.2018.00306 |
identifier_str_mv |
BARROS, B. D. F. et al. Mutation detection in tumor-derived cell free DNA anticipates progression in a patient with metastatic colorectal cancer. Front. Oncol., v. 8, p. 306, ago/2018. 10.3389/fonc.2018.00306 |
url |
https://repositorio.ufrn.br/jspui/handle/123456789/25924 |
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eng |
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eng |
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openAccess |
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