Case Report: BAP1 Mutation and RAD21 Amplification as Predictive Biomarkers to PARP Inhibitor in Metastatic Intrahepatic Cholangiocarcinoma
IntroductionIntrahepatic cholangiocarcinoma (ICC) is a rare hepatobiliary cancer characterized by a poor prognosis and a limited response to conventional therapies. Currently chemotherapy is the only therapeutic option for patients with Stage IV ICC. Due to the poor response rate, there is an urgent...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.567289/full |
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| author | Francesco Sabbatino Francesco Sabbatino Luigi Liguori Umberto Malapelle Francesca Schiavi Vincenzo Tortora Valeria Conti Valeria Conti Amelia Filippelli Amelia Filippelli Giampaolo Tortora Cristina R. Ferrone Stefano Pepe Stefano Pepe |
| author_facet | Francesco Sabbatino Francesco Sabbatino Luigi Liguori Umberto Malapelle Francesca Schiavi Vincenzo Tortora Valeria Conti Valeria Conti Amelia Filippelli Amelia Filippelli Giampaolo Tortora Cristina R. Ferrone Stefano Pepe Stefano Pepe |
| author_sort | Francesco Sabbatino |
| collection | DOAJ |
| description | IntroductionIntrahepatic cholangiocarcinoma (ICC) is a rare hepatobiliary cancer characterized by a poor prognosis and a limited response to conventional therapies. Currently chemotherapy is the only therapeutic option for patients with Stage IV ICC. Due to the poor response rate, there is an urgent need to identify novel molecular targets to develop novel effective therapies. Precision oncology tests utilizing targeted next-generation sequencing (NGS) platforms have rapidly entered into clinical practice. Profiling the genome and transcriptome of cancer to identify potentially targetable oncogenic pathways may guide the clinical care of the patient.Case presentationWe present a 56-year-old male patient affected with metastatic ICC, whose cancer underwent several precision oncology tests by different NGS platforms. A novel BAP1 mutation (splice site c.581-17_585del22) and a RAD21 amplification were identified by a commercial available platform on a metastatic lesion. No germline BAP1 mutations were identified. Several lines of evidences indicate that PARP inhibitor administration might be an effective treatment in presence of BAP1 and/or RAD21 alterations since both BAP1 and RAD21 are involved in the DNA repair pathway, BAP1 interacts with BRCA1 and BRCA1-mediated DNA repair pathway alterations enhance the sensitivity to PARP inhibitor administration. In this case, after failing conventional therapies, patient was treated with PARP inhibitor olaparib. The patient had a partial response according to RECIST criteria with an overall survival of 37.2 months from the time of diagnosis of his ICC. Following 11.0 months on olaparib treatment, sustained stable disease control is ongoing. The patient is still being treated with olaparib and no significant toxicity has been reported.ConclusionThese findings have clinical relevance since we have shown PARP inhibitor as a potential treatment for ICC patients harboring BAP1 deletion and RAD21 amplification. We have also highlighted the utility of NGS platforms to identify targetable mutations within a cancer. |
| first_indexed | 2024-12-21T14:32:36Z |
| format | Article |
| id | doaj.art-99a02493350d41458998a976d2c3a8fd |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-21T14:32:36Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-99a02493350d41458998a976d2c3a8fd2022-12-21T19:00:27ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-11-011010.3389/fonc.2020.567289567289Case Report: BAP1 Mutation and RAD21 Amplification as Predictive Biomarkers to PARP Inhibitor in Metastatic Intrahepatic CholangiocarcinomaFrancesco Sabbatino0Francesco Sabbatino1Luigi Liguori2Umberto Malapelle3Francesca Schiavi4Vincenzo Tortora5Valeria Conti6Valeria Conti7Amelia Filippelli8Amelia Filippelli9Giampaolo Tortora10Cristina R. Ferrone11Stefano Pepe12Stefano Pepe13Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Salerno, ItalyOncology Unit, University Hospital San Giovanni di Dio e Ruggi D’Aragona, Salerno, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, ItalyPublic Health, University of Naples “Federico II”, Naples, ItalyFamilial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology IOV–IRCCS, Padua, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, ItalyDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Salerno, ItalyClinical Pharmacology and Pharmacogenetics Unit, University Hospital “San Giovanni di Dio e Ruggi D’Aragona”, Salerno, ItalyDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Salerno, ItalyClinical Pharmacology and Pharmacogenetics Unit, University Hospital “San Giovanni di Dio e Ruggi D’Aragona”, Salerno, ItalyOncologia Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Del Sacro Cuore, Roma, ItalyDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Salerno, ItalyOncology Unit, University Hospital San Giovanni di Dio e Ruggi D’Aragona, Salerno, ItalyIntroductionIntrahepatic cholangiocarcinoma (ICC) is a rare hepatobiliary cancer characterized by a poor prognosis and a limited response to conventional therapies. Currently chemotherapy is the only therapeutic option for patients with Stage IV ICC. Due to the poor response rate, there is an urgent need to identify novel molecular targets to develop novel effective therapies. Precision oncology tests utilizing targeted next-generation sequencing (NGS) platforms have rapidly entered into clinical practice. Profiling the genome and transcriptome of cancer to identify potentially targetable oncogenic pathways may guide the clinical care of the patient.Case presentationWe present a 56-year-old male patient affected with metastatic ICC, whose cancer underwent several precision oncology tests by different NGS platforms. A novel BAP1 mutation (splice site c.581-17_585del22) and a RAD21 amplification were identified by a commercial available platform on a metastatic lesion. No germline BAP1 mutations were identified. Several lines of evidences indicate that PARP inhibitor administration might be an effective treatment in presence of BAP1 and/or RAD21 alterations since both BAP1 and RAD21 are involved in the DNA repair pathway, BAP1 interacts with BRCA1 and BRCA1-mediated DNA repair pathway alterations enhance the sensitivity to PARP inhibitor administration. In this case, after failing conventional therapies, patient was treated with PARP inhibitor olaparib. The patient had a partial response according to RECIST criteria with an overall survival of 37.2 months from the time of diagnosis of his ICC. Following 11.0 months on olaparib treatment, sustained stable disease control is ongoing. The patient is still being treated with olaparib and no significant toxicity has been reported.ConclusionThese findings have clinical relevance since we have shown PARP inhibitor as a potential treatment for ICC patients harboring BAP1 deletion and RAD21 amplification. We have also highlighted the utility of NGS platforms to identify targetable mutations within a cancer.https://www.frontiersin.org/articles/10.3389/fonc.2020.567289/fullBAP1precision oncologycholangio carcinomaPoly ADP ribose polymerase (PARP) inhibitorRAD21olaparib |
| spellingShingle | Francesco Sabbatino Francesco Sabbatino Luigi Liguori Umberto Malapelle Francesca Schiavi Vincenzo Tortora Valeria Conti Valeria Conti Amelia Filippelli Amelia Filippelli Giampaolo Tortora Cristina R. Ferrone Stefano Pepe Stefano Pepe Case Report: BAP1 Mutation and RAD21 Amplification as Predictive Biomarkers to PARP Inhibitor in Metastatic Intrahepatic Cholangiocarcinoma Frontiers in Oncology BAP1 precision oncology cholangio carcinoma Poly ADP ribose polymerase (PARP) inhibitor RAD21 olaparib |
| title | Case Report: BAP1 Mutation and RAD21 Amplification as Predictive Biomarkers to PARP Inhibitor in Metastatic Intrahepatic Cholangiocarcinoma |
| title_full | Case Report: BAP1 Mutation and RAD21 Amplification as Predictive Biomarkers to PARP Inhibitor in Metastatic Intrahepatic Cholangiocarcinoma |
| title_fullStr | Case Report: BAP1 Mutation and RAD21 Amplification as Predictive Biomarkers to PARP Inhibitor in Metastatic Intrahepatic Cholangiocarcinoma |
| title_full_unstemmed | Case Report: BAP1 Mutation and RAD21 Amplification as Predictive Biomarkers to PARP Inhibitor in Metastatic Intrahepatic Cholangiocarcinoma |
| title_short | Case Report: BAP1 Mutation and RAD21 Amplification as Predictive Biomarkers to PARP Inhibitor in Metastatic Intrahepatic Cholangiocarcinoma |
| title_sort | case report bap1 mutation and rad21 amplification as predictive biomarkers to parp inhibitor in metastatic intrahepatic cholangiocarcinoma |
| topic | BAP1 precision oncology cholangio carcinoma Poly ADP ribose polymerase (PARP) inhibitor RAD21 olaparib |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.567289/full |
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