Publicação
Clinical implications of PIK3CA mutations in gliomas molecular subgroups
| Resumo: | Gliomas are the most common and lethal malignant tumors of central nervous system. In 2016, World Health Organization (WHO) classification included IDH mutations and 1p/19q codeletion as a diagnostic criteria to define gliomas. However new biomarkers of diagnosis, prognosis and response to therapy are needed. In this context, PIK3CA mutations have been described as constitutive mutations seeming to be a good therapeutic target. Our objective was to clarify the clinical importance of PIK3CA mutations according to the 2016 WHO classification, as well as the impact of several biomarkers on diagnosis, prognosis and response to therapy in 437 glioma samples. According to the multivariate analysis performed, gliomas molecular subgroups have higher prognostic value than histological subgroups (P<0.001). PTEN deletions were considered prognostic factors of poor outcomes in astrocytomas IDH wildtype, while in GBM IDH wildtype were associated with better prognosis. On opposite, EGFR amplification and TERT mutations had no impact in the overall survival of patients. We verified that EGFR amplification had a predictive value of response to radiotherapy (P=0.007). PIK3CA mutations were most common in IDH mutant + 1p/19q codeletion (oligodendrogliomas) (10%). H1047R and E542K were the most frequent mutations identified in the remaining gliomas molecular subgroups. Importantly, we found 3 unreported pathogenic variants in exon 20 of PIK3CA (c.3112T>C, c.2988T>C, c.3040C>T) and one polymorphic variant (c.3210A>G). For the first time, it was identified the rs45455192 polymorphism (16% - 24%) in the different gliomas molecular subgroups, although this polymorphism did not showed prognostic value. The recurrences analysis demonstrated that PIK3CA mutations constitute early events maintained during tumor progression. Overall, this study showed molecular classification is a more accurate method to predict clinical outcome and despite PIK3CA mutations being present at low frequency in gliomas, they seem to be important for tumor progression. |
|---|---|
| Autores principais: | Brito, Cheila Martins |
| Assunto: | Gliomas PIK3CA mutations 2016 WHO classification therapeutic target |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| _version_ | 1868983223854301184 |
|---|---|
| author | Brito, Cheila Martins |
| author_facet | Brito, Cheila Martins |
| author_role | author |
| contributor_name_str_mv | Sousa, Marta Roque, Maria Lúcia RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Brito, Cheila Martins\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Sousa, Marta Roque, Maria Lúcia RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Brito, Cheila Martins |
| datacite.date.Accepted.fl_str_mv | 2018-11-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2019-01-21T13:52:46Z |
| datacite.date.embargoed.fl_str_mv | 2019-01-21T13:52:46Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Gliomas PIK3CA mutations 2016 WHO classification therapeutic target |
| datacite.titles.title.fl_str_mv | Clinical implications of PIK3CA mutations in gliomas molecular subgroups |
| dc.contributor.none.fl_str_mv | Sousa, Marta Roque, Maria Lúcia RUN |
| dc.creator.none.fl_str_mv | Brito, Cheila Martins |
| dc.date.Accepted.fl_str_mv | 2018-11-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2019-01-21T13:52:46Z |
| dc.date.embargoed.fl_str_mv | 2019-01-21T13:52:46Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/58097 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Gliomas PIK3CA mutations 2016 WHO classification therapeutic target |
| dc.title.fl_str_mv | Clinical implications of PIK3CA mutations in gliomas molecular subgroups |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_bdcc |
| description | Gliomas are the most common and lethal malignant tumors of central nervous system. In 2016, World Health Organization (WHO) classification included IDH mutations and 1p/19q codeletion as a diagnostic criteria to define gliomas. However new biomarkers of diagnosis, prognosis and response to therapy are needed. In this context, PIK3CA mutations have been described as constitutive mutations seeming to be a good therapeutic target. Our objective was to clarify the clinical importance of PIK3CA mutations according to the 2016 WHO classification, as well as the impact of several biomarkers on diagnosis, prognosis and response to therapy in 437 glioma samples. According to the multivariate analysis performed, gliomas molecular subgroups have higher prognostic value than histological subgroups (P<0.001). PTEN deletions were considered prognostic factors of poor outcomes in astrocytomas IDH wildtype, while in GBM IDH wildtype were associated with better prognosis. On opposite, EGFR amplification and TERT mutations had no impact in the overall survival of patients. We verified that EGFR amplification had a predictive value of response to radiotherapy (P=0.007). PIK3CA mutations were most common in IDH mutant + 1p/19q codeletion (oligodendrogliomas) (10%). H1047R and E542K were the most frequent mutations identified in the remaining gliomas molecular subgroups. Importantly, we found 3 unreported pathogenic variants in exon 20 of PIK3CA (c.3112T>C, c.2988T>C, c.3040C>T) and one polymorphic variant (c.3210A>G). For the first time, it was identified the rs45455192 polymorphism (16% - 24%) in the different gliomas molecular subgroups, although this polymorphism did not showed prognostic value. The recurrences analysis demonstrated that PIK3CA mutations constitute early events maintained during tumor progression. Overall, this study showed molecular classification is a more accurate method to predict clinical outcome and despite PIK3CA mutations being present at low frequency in gliomas, they seem to be important for tumor progression. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | masterThesis |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/e67a4dee-1651-4dce-bbc6-13ef7d5a5649/download |
| id | run_197396980fec005520c8d8afa0125a8c |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/58097 |
| inst_facet_str | urn:organizationAcronym:unl{{{_:::_}}}Universidade Nova de Lisboa |
| instacron_str | unl |
| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
| network_acronym_str | run |
| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/58097 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Brito, Cheila Martins |
| publishDate | 2018 |
| repo_facet_str | urn:repositoryAcronym:run{{{_:::_}}}Repositório Institucional da UNL |
| reponame_str | Repositório Institucional da UNL |
| repository_id_str | urn:repositoryAcronym:run |
| service_str_mv | urn:repositoryAcronym:run |
| spelling | engpt_PTGliomas are the most common and lethal malignant tumors of central nervous system. In 2016, World Health Organization (WHO) classification included IDH mutations and 1p/19q codeletion as a diagnostic criteria to define gliomas. However new biomarkers of diagnosis, prognosis and response to therapy are needed. In this context, PIK3CA mutations have been described as constitutive mutations seeming to be a good therapeutic target. Our objective was to clarify the clinical importance of PIK3CA mutations according to the 2016 WHO classification, as well as the impact of several biomarkers on diagnosis, prognosis and response to therapy in 437 glioma samples. According to the multivariate analysis performed, gliomas molecular subgroups have higher prognostic value than histological subgroups (P<0.001). PTEN deletions were considered prognostic factors of poor outcomes in astrocytomas IDH wildtype, while in GBM IDH wildtype were associated with better prognosis. On opposite, EGFR amplification and TERT mutations had no impact in the overall survival of patients. We verified that EGFR amplification had a predictive value of response to radiotherapy (P=0.007). PIK3CA mutations were most common in IDH mutant + 1p/19q codeletion (oligodendrogliomas) (10%). H1047R and E542K were the most frequent mutations identified in the remaining gliomas molecular subgroups. Importantly, we found 3 unreported pathogenic variants in exon 20 of PIK3CA (c.3112T>C, c.2988T>C, c.3040C>T) and one polymorphic variant (c.3210A>G). For the first time, it was identified the rs45455192 polymorphism (16% - 24%) in the different gliomas molecular subgroups, although this polymorphism did not showed prognostic value. The recurrences analysis demonstrated that PIK3CA mutations constitute early events maintained during tumor progression. Overall, this study showed molecular classification is a more accurate method to predict clinical outcome and despite PIK3CA mutations being present at low frequency in gliomas, they seem to be important for tumor progression.application/pdfpt_PTClinical implications of PIK3CA mutations in gliomas molecular subgroupsBrito, Cheila MartinsSousa, MartaRoque, Maria LúciaHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.pt2019-01-21T13:52:46Z2018-1120182018-11-01T00:00:00ZHandlehttp://hdl.handle.net/10362/58097http://purl.org/coar/access_right/c_abf2open accessGliomasPIK3CAmutations2016 WHO classificationtherapeutic target2207759 bytesliteraturehttp://purl.org/coar/resource_type/c_bdccmaster thesishttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/e67a4dee-1651-4dce-bbc6-13ef7d5a5649/download |
| spellingShingle | Clinical implications of PIK3CA mutations in gliomas molecular subgroups Brito, Cheila Martins Gliomas PIK3CA mutations 2016 WHO classification therapeutic target |
| status | SINGLETON |
| subject.fl_str_mv | Gliomas PIK3CA mutations 2016 WHO classification therapeutic target |
| title | Clinical implications of PIK3CA mutations in gliomas molecular subgroups |
| title_full | Clinical implications of PIK3CA mutations in gliomas molecular subgroups |
| title_fullStr | Clinical implications of PIK3CA mutations in gliomas molecular subgroups |
| title_full_unstemmed | Clinical implications of PIK3CA mutations in gliomas molecular subgroups |
| title_short | Clinical implications of PIK3CA mutations in gliomas molecular subgroups |
| title_sort | Clinical implications of PIK3CA mutations in gliomas molecular subgroups |
| topic | Gliomas PIK3CA mutations 2016 WHO classification therapeutic target |
| topic_facet | Gliomas PIK3CA mutations 2016 WHO classification therapeutic target |
| url | http://hdl.handle.net/10362/58097 |
| visible | 1 |