Inflammatory breast cancer: Clinical implications of genomic alterations and mutational profiling
Autor(a) principal: | |
---|---|
Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/cancers12102816 http://hdl.handle.net/11449/206598 |
Resumo: | Inflammatory breast cancer (IBC) is a rare and aggressive type of breast cancer whose molecular basis is poorly understood. We performed a comprehensive molecular analysis of 24 IBC biopsies naïve of treatment, using a high-resolution microarray platform and targeted next-generation sequencing (105 cancer-related genes). The genes more frequently affected by gains were MYC (75%) and MDM4 (71%), while frequent losses encompassed TP53 (71%) and RB1 (58%). Increased MYC and MDM4 protein expression levels were detected in 18 cases. These genes have been related to IBC aggressiveness, and MDM4 is a potential therapeutic target in IBC. Functional enrichment analysis revealed genes associated with inflammatory regulation and immune response. High homologous recombination (HR) deficiency scores were detected in triple-negative and metastatic IBC cases. A high telomeric allelic imbalance score was found in patients having worse overall survival (OS). The mutational profiling was compared with non-IBC (TCGA, n = 250) and IBC (n = 118) from four datasets, validating our findings. Higher frequency of TP53 and BRCA2 variants were detected compared to non-IBC, while PIKC3A showed similar frequency. Variants in mismatch repair and HR genes were associated with worse OS. Our study provided a framework for improved diagnosis and therapeutic alternatives for this aggressive tumor type. |
id |
UNSP_58fc13d3a32fa7467e7ead73217b9143 |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/206598 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
spelling |
Inflammatory breast cancer: Clinical implications of genomic alterations and mutational profilingCopy number alterationsGene variantsGenomic scarsHomologous recombination deficiencyInflammatory breast cancerMicroarrayInflammatory breast cancer (IBC) is a rare and aggressive type of breast cancer whose molecular basis is poorly understood. We performed a comprehensive molecular analysis of 24 IBC biopsies naïve of treatment, using a high-resolution microarray platform and targeted next-generation sequencing (105 cancer-related genes). The genes more frequently affected by gains were MYC (75%) and MDM4 (71%), while frequent losses encompassed TP53 (71%) and RB1 (58%). Increased MYC and MDM4 protein expression levels were detected in 18 cases. These genes have been related to IBC aggressiveness, and MDM4 is a potential therapeutic target in IBC. Functional enrichment analysis revealed genes associated with inflammatory regulation and immune response. High homologous recombination (HR) deficiency scores were detected in triple-negative and metastatic IBC cases. A high telomeric allelic imbalance score was found in patients having worse overall survival (OS). The mutational profiling was compared with non-IBC (TCGA, n = 250) and IBC (n = 118) from four datasets, validating our findings. Higher frequency of TP53 and BRCA2 variants were detected compared to non-IBC, while PIKC3A showed similar frequency. Variants in mismatch repair and HR genes were associated with worse OS. Our study provided a framework for improved diagnosis and therapeutic alternatives for this aggressive tumor type.International Research Center A.C.Camargo Cancer CenterDepartment of Clinical Genetics University Hospital of Southern DenmarkDepartment of Genetics and Morphology Institute of Biological Sciences University of Brasília-UnBDepartment of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science São Paulo State University-UNESPDepartment of Structural and Functional Biology Institute of Biosciences São Paulo State University-UNESPDepartment of Mathematics and Computer Science University of Southern DenmarkDepartment of Breast and Gynecologic Oncology Barretos Cancer Hospital Pio XII FoundationMolecular Oncology Research CenterDepartment of Pathology A.C.Camargo Cancer CenterTUM School of Life Sciences Weihenstephan Technical University of MunichInstitute of Regional Health Research University of Southern DenmarkDiagnósticos da América (DASA)Department of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science São Paulo State University-UNESPDepartment of Structural and Functional Biology Institute of Biosciences São Paulo State University-UNESPA.C.Camargo Cancer CenterUniversity Hospital of Southern DenmarkUniversity of Brasília-UnBUniversidade Estadual Paulista (Unesp)University of Southern DenmarkPio XII FoundationMolecular Oncology Research CenterTechnical University of MunichDiagnósticos da América (DASA)Faldoni, Flávia L. C.Villacis, Rolando A. R.Canto, Luisa M.Fonseca-Alves, Carlos E. [UNESP]Cury, Sarah S. [UNESP]Larsen, Simon J.Aagaard, Mads M.Souza, Cristiano P.Scapulatempo-Neto, CristovamOsório, Cynthia A. B. T.Baumbach, JanMarchi, Fabio A.Rogatto, Silvia R.2021-06-25T10:34:59Z2021-06-25T10:34:59Z2020-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1-21http://dx.doi.org/10.3390/cancers12102816Cancers, v. 12, n. 10, p. 1-21, 2020.2072-6694http://hdl.handle.net/11449/20659810.3390/cancers121028162-s2.0-85091873438Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengCancersinfo:eu-repo/semantics/openAccess2021-10-23T07:59:05Zoai:repositorio.unesp.br:11449/206598Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:36:40.179425Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Inflammatory breast cancer: Clinical implications of genomic alterations and mutational profiling |
title |
Inflammatory breast cancer: Clinical implications of genomic alterations and mutational profiling |
spellingShingle |
Inflammatory breast cancer: Clinical implications of genomic alterations and mutational profiling Faldoni, Flávia L. C. Copy number alterations Gene variants Genomic scars Homologous recombination deficiency Inflammatory breast cancer Microarray |
title_short |
Inflammatory breast cancer: Clinical implications of genomic alterations and mutational profiling |
title_full |
Inflammatory breast cancer: Clinical implications of genomic alterations and mutational profiling |
title_fullStr |
Inflammatory breast cancer: Clinical implications of genomic alterations and mutational profiling |
title_full_unstemmed |
Inflammatory breast cancer: Clinical implications of genomic alterations and mutational profiling |
title_sort |
Inflammatory breast cancer: Clinical implications of genomic alterations and mutational profiling |
author |
Faldoni, Flávia L. C. |
author_facet |
Faldoni, Flávia L. C. Villacis, Rolando A. R. Canto, Luisa M. Fonseca-Alves, Carlos E. [UNESP] Cury, Sarah S. [UNESP] Larsen, Simon J. Aagaard, Mads M. Souza, Cristiano P. Scapulatempo-Neto, Cristovam Osório, Cynthia A. B. T. Baumbach, Jan Marchi, Fabio A. Rogatto, Silvia R. |
author_role |
author |
author2 |
Villacis, Rolando A. R. Canto, Luisa M. Fonseca-Alves, Carlos E. [UNESP] Cury, Sarah S. [UNESP] Larsen, Simon J. Aagaard, Mads M. Souza, Cristiano P. Scapulatempo-Neto, Cristovam Osório, Cynthia A. B. T. Baumbach, Jan Marchi, Fabio A. Rogatto, Silvia R. |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
A.C.Camargo Cancer Center University Hospital of Southern Denmark University of Brasília-UnB Universidade Estadual Paulista (Unesp) University of Southern Denmark Pio XII Foundation Molecular Oncology Research Center Technical University of Munich Diagnósticos da América (DASA) |
dc.contributor.author.fl_str_mv |
Faldoni, Flávia L. C. Villacis, Rolando A. R. Canto, Luisa M. Fonseca-Alves, Carlos E. [UNESP] Cury, Sarah S. [UNESP] Larsen, Simon J. Aagaard, Mads M. Souza, Cristiano P. Scapulatempo-Neto, Cristovam Osório, Cynthia A. B. T. Baumbach, Jan Marchi, Fabio A. Rogatto, Silvia R. |
dc.subject.por.fl_str_mv |
Copy number alterations Gene variants Genomic scars Homologous recombination deficiency Inflammatory breast cancer Microarray |
topic |
Copy number alterations Gene variants Genomic scars Homologous recombination deficiency Inflammatory breast cancer Microarray |
description |
Inflammatory breast cancer (IBC) is a rare and aggressive type of breast cancer whose molecular basis is poorly understood. We performed a comprehensive molecular analysis of 24 IBC biopsies naïve of treatment, using a high-resolution microarray platform and targeted next-generation sequencing (105 cancer-related genes). The genes more frequently affected by gains were MYC (75%) and MDM4 (71%), while frequent losses encompassed TP53 (71%) and RB1 (58%). Increased MYC and MDM4 protein expression levels were detected in 18 cases. These genes have been related to IBC aggressiveness, and MDM4 is a potential therapeutic target in IBC. Functional enrichment analysis revealed genes associated with inflammatory regulation and immune response. High homologous recombination (HR) deficiency scores were detected in triple-negative and metastatic IBC cases. A high telomeric allelic imbalance score was found in patients having worse overall survival (OS). The mutational profiling was compared with non-IBC (TCGA, n = 250) and IBC (n = 118) from four datasets, validating our findings. Higher frequency of TP53 and BRCA2 variants were detected compared to non-IBC, while PIKC3A showed similar frequency. Variants in mismatch repair and HR genes were associated with worse OS. Our study provided a framework for improved diagnosis and therapeutic alternatives for this aggressive tumor type. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-10-01 2021-06-25T10:34:59Z 2021-06-25T10:34:59Z |
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/10.3390/cancers12102816 Cancers, v. 12, n. 10, p. 1-21, 2020. 2072-6694 http://hdl.handle.net/11449/206598 10.3390/cancers12102816 2-s2.0-85091873438 |
url |
http://dx.doi.org/10.3390/cancers12102816 http://hdl.handle.net/11449/206598 |
identifier_str_mv |
Cancers, v. 12, n. 10, p. 1-21, 2020. 2072-6694 10.3390/cancers12102816 2-s2.0-85091873438 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Cancers |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1-21 |
dc.source.none.fl_str_mv |
Scopus 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 |
|
_version_ |
1808129340969320448 |