PIK3CA activating mutations are associated with more disseminated disease at presentation and earlier recurrence in glioblastoma
Abstract Phosphatidylinositol 3-kinase signaling promotes cell growth and survival and is frequently activated in infiltrative gliomas. Activating mutations in PIK3CA gene are observed in 6–15% of glioblastomas, although their clinical significance is largely undescribed. The objective of this study...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-04-01
|
| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40478-019-0720-8 |
| _version_ | 1818032463931244544 |
|---|---|
| author | Shota Tanaka Tracy T. Batchelor A. John Iafrate Dora Dias-Santagata Darrell R. Borger Leif W. Ellisen Daniel Yang David N. Louis Daniel P. Cahill Andrew S. Chi |
| author_facet | Shota Tanaka Tracy T. Batchelor A. John Iafrate Dora Dias-Santagata Darrell R. Borger Leif W. Ellisen Daniel Yang David N. Louis Daniel P. Cahill Andrew S. Chi |
| author_sort | Shota Tanaka |
| collection | DOAJ |
| description | Abstract Phosphatidylinositol 3-kinase signaling promotes cell growth and survival and is frequently activated in infiltrative gliomas. Activating mutations in PIK3CA gene are observed in 6–15% of glioblastomas, although their clinical significance is largely undescribed. The objective of this study was to examine whether PIK3CA mutations are associated with a specific clinical phenotype in glioblastoma. We retrospectively reviewed 157 consecutive newly diagnosed glioblastoma patients from December 2009 to June 2012 who underwent molecular profiling consisting of targeted hotspot genotyping, fluorescence in situ hybridization for gene amplification, and methylation-specific PCR for O6-methylguanine-DNA methyltransferase promoter methylation. Molecular alterations were correlated with clinical features, imaging and outcome. The Cancer Genome Atlas data was analyzed as a validation set. There were 91 males; median age was 58 years (range, 23–85). With a median follow-up of 20.9 months, median progression-free survival (PFS) and estimated overall survival (OS) were 11.9 and 24.0 months, respectively. Thirteen patients (8.3%) harbored PIK3CA mutation, which was associated with younger age (mean 49.4 vs. 58.1 years, p = 0.02). PIK3CA mutation correlated with shorter PFS (median 6.9 vs. 12.4 months, p = 0.01) and OS (median 21.2 vs. 24.2 months, p = 0.049) in multivariate analysis. A significant association between PIK3CA mutation and more disseminated disease at diagnosis, as defined by gliomatosis, multicentric lesions, or distant leptomeningeal lesions, was observed (46.2% vs. 11.1%, p = 0.004). In conclusion, despite the association with younger age, PIK3CA activating mutations are associated with earlier recurrence and shorter survival in adult glioblastoma. The aggressive course of these tumors may be related to their propensity for disseminated presentation. |
| first_indexed | 2024-12-10T06:07:47Z |
| format | Article |
| id | doaj.art-9b32b0e049694cab8a5749e82076e225 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-12-10T06:07:47Z |
| publishDate | 2019-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-9b32b0e049694cab8a5749e82076e2252022-12-22T01:59:39ZengBMCActa Neuropathologica Communications2051-59602019-04-01711810.1186/s40478-019-0720-8PIK3CA activating mutations are associated with more disseminated disease at presentation and earlier recurrence in glioblastomaShota Tanaka0Tracy T. Batchelor1A. John Iafrate2Dora Dias-Santagata3Darrell R. Borger4Leif W. Ellisen5Daniel Yang6David N. Louis7Daniel P. Cahill8Andrew S. Chi9Stephen E. and Catherine Pappas Center for Neuro-Oncology, Department of NeurologyStephen E. and Catherine Pappas Center for Neuro-Oncology, Department of NeurologyTranslational Research Laboratory, Cancer CenterTranslational Research Laboratory, Cancer CenterTranslational Research Laboratory, Cancer CenterMassachusetts General Hospital Cancer Center, Harvard Medical SchoolStephen E. and Catherine Pappas Center for Neuro-Oncology, Department of NeurologyDepartment of PathologyDepartment of NeurosurgeryPerlmutter Cancer Center, New York University Langone Health and School of MedicineAbstract Phosphatidylinositol 3-kinase signaling promotes cell growth and survival and is frequently activated in infiltrative gliomas. Activating mutations in PIK3CA gene are observed in 6–15% of glioblastomas, although their clinical significance is largely undescribed. The objective of this study was to examine whether PIK3CA mutations are associated with a specific clinical phenotype in glioblastoma. We retrospectively reviewed 157 consecutive newly diagnosed glioblastoma patients from December 2009 to June 2012 who underwent molecular profiling consisting of targeted hotspot genotyping, fluorescence in situ hybridization for gene amplification, and methylation-specific PCR for O6-methylguanine-DNA methyltransferase promoter methylation. Molecular alterations were correlated with clinical features, imaging and outcome. The Cancer Genome Atlas data was analyzed as a validation set. There were 91 males; median age was 58 years (range, 23–85). With a median follow-up of 20.9 months, median progression-free survival (PFS) and estimated overall survival (OS) were 11.9 and 24.0 months, respectively. Thirteen patients (8.3%) harbored PIK3CA mutation, which was associated with younger age (mean 49.4 vs. 58.1 years, p = 0.02). PIK3CA mutation correlated with shorter PFS (median 6.9 vs. 12.4 months, p = 0.01) and OS (median 21.2 vs. 24.2 months, p = 0.049) in multivariate analysis. A significant association between PIK3CA mutation and more disseminated disease at diagnosis, as defined by gliomatosis, multicentric lesions, or distant leptomeningeal lesions, was observed (46.2% vs. 11.1%, p = 0.004). In conclusion, despite the association with younger age, PIK3CA activating mutations are associated with earlier recurrence and shorter survival in adult glioblastoma. The aggressive course of these tumors may be related to their propensity for disseminated presentation.http://link.springer.com/article/10.1186/s40478-019-0720-8DisseminationGlioblastomaGliomatosisMulticentricPIK3CA |
| spellingShingle | Shota Tanaka Tracy T. Batchelor A. John Iafrate Dora Dias-Santagata Darrell R. Borger Leif W. Ellisen Daniel Yang David N. Louis Daniel P. Cahill Andrew S. Chi PIK3CA activating mutations are associated with more disseminated disease at presentation and earlier recurrence in glioblastoma Acta Neuropathologica Communications Dissemination Glioblastoma Gliomatosis Multicentric PIK3CA |
| title | PIK3CA activating mutations are associated with more disseminated disease at presentation and earlier recurrence in glioblastoma |
| title_full | PIK3CA activating mutations are associated with more disseminated disease at presentation and earlier recurrence in glioblastoma |
| title_fullStr | PIK3CA activating mutations are associated with more disseminated disease at presentation and earlier recurrence in glioblastoma |
| title_full_unstemmed | PIK3CA activating mutations are associated with more disseminated disease at presentation and earlier recurrence in glioblastoma |
| title_short | PIK3CA activating mutations are associated with more disseminated disease at presentation and earlier recurrence in glioblastoma |
| title_sort | pik3ca activating mutations are associated with more disseminated disease at presentation and earlier recurrence in glioblastoma |
| topic | Dissemination Glioblastoma Gliomatosis Multicentric PIK3CA |
| url | http://link.springer.com/article/10.1186/s40478-019-0720-8 |
| work_keys_str_mv | AT shotatanaka pik3caactivatingmutationsareassociatedwithmoredisseminateddiseaseatpresentationandearlierrecurrenceinglioblastoma AT tracytbatchelor pik3caactivatingmutationsareassociatedwithmoredisseminateddiseaseatpresentationandearlierrecurrenceinglioblastoma AT ajohniafrate pik3caactivatingmutationsareassociatedwithmoredisseminateddiseaseatpresentationandearlierrecurrenceinglioblastoma AT doradiassantagata pik3caactivatingmutationsareassociatedwithmoredisseminateddiseaseatpresentationandearlierrecurrenceinglioblastoma AT darrellrborger pik3caactivatingmutationsareassociatedwithmoredisseminateddiseaseatpresentationandearlierrecurrenceinglioblastoma AT leifwellisen pik3caactivatingmutationsareassociatedwithmoredisseminateddiseaseatpresentationandearlierrecurrenceinglioblastoma AT danielyang pik3caactivatingmutationsareassociatedwithmoredisseminateddiseaseatpresentationandearlierrecurrenceinglioblastoma AT davidnlouis pik3caactivatingmutationsareassociatedwithmoredisseminateddiseaseatpresentationandearlierrecurrenceinglioblastoma AT danielpcahill pik3caactivatingmutationsareassociatedwithmoredisseminateddiseaseatpresentationandearlierrecurrenceinglioblastoma AT andrewschi pik3caactivatingmutationsareassociatedwithmoredisseminateddiseaseatpresentationandearlierrecurrenceinglioblastoma |