Unraveling the Mystery: Next Generation Sequencing Sheds Light on Neuroblastoma Pathogenesis and Targeted Therapies
Background: There is considerable interest in the molecular evaluation of solid tumors in pediatric cases. Although clinical trials are in progress for targeted therapies against neuroblastoma (NB), novel therapeutic strategies are needed for high-risk cases that are resistant to therapy. The aim of...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IMR Press
2023-08-01
|
| Series: | Frontiers in Bioscience-Landmark |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/FBL/28/8/10.31083/j.fbl2808171 |
| _version_ | 1827825265708892160 |
|---|---|
| author | Tekincan Aktas Deniz Kızmazoglu Safiye Aktas Aylin Erol Efe Serinan Ozde Gokbayrak Sefayi Merve Ozdemir Zekiye Altun Erdener Ozer Emre Cecen Dilek Ince Nur Olgun |
| author_facet | Tekincan Aktas Deniz Kızmazoglu Safiye Aktas Aylin Erol Efe Serinan Ozde Gokbayrak Sefayi Merve Ozdemir Zekiye Altun Erdener Ozer Emre Cecen Dilek Ince Nur Olgun |
| author_sort | Tekincan Aktas |
| collection | DOAJ |
| description | Background: There is considerable interest in the molecular evaluation of solid tumors in pediatric cases. Although clinical trials are in progress for targeted therapies against neuroblastoma (NB), novel therapeutic strategies are needed for high-risk cases that are resistant to therapy. The aim of the present study was to document the specific gene mutations related to targeted therapy in relapsed or refractory NB patients by using next generation sequencing (NGS). Methods: The study included 57 NB patients from amongst 1965 neuroblastic cases in Turkey who experienced a recurrence after multi-model therapy. The cases were diagnosed, risk-stratified, and treated according to the classification system from the International Neuroblastoma Risk Group. Single nucleotide variations in 60 genes were investigated using the Pillar Onco/Reveal Multicancer v4 panel and Pillar RNA fusion panel on the Illumina Miniseq platform. Results: ERBB2 I655V was the most frequent mutation and was found in 39.65% of cases. Anaplastic Lymphoma Kinase (ALK) mutations (F1174L, R1275Q, and rare mutations in the tyrosine kinase domain) were detected in 29.3% of cases. Fusion mutations in NTRK1, NTRK3, ROS1, RET, FGFR3, ALK and BRAF were observed in 19.6% of cases. Conclusions: This study presents valuable mutation data for relapsed and refractory NB patients. The high frequency of the ERBB2 I655V mutation may allow further exploration of this mutation as a potential therapeutic target. Rare BRAF mutations may also provide opportunities for targeted therapy. The role of ABL1 mutations in NB should also be explored further. |
| first_indexed | 2024-03-12T02:39:40Z |
| format | Article |
| id | doaj.art-cae3b7f44c3c4b56af1d9bf80e429136 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-03-12T02:39:40Z |
| publishDate | 2023-08-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-cae3b7f44c3c4b56af1d9bf80e4291362023-09-04T09:13:42ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-08-0128817110.31083/j.fbl2808171S2768-6701(23)00991-7Unraveling the Mystery: Next Generation Sequencing Sheds Light on Neuroblastoma Pathogenesis and Targeted TherapiesTekincan Aktas0Deniz Kızmazoglu1Safiye Aktas2Aylin Erol3Efe Serinan4Ozde Gokbayrak5Sefayi Merve Ozdemir6Zekiye Altun7Erdener Ozer8Emre Cecen9Dilek Ince10Nur Olgun11Department of Basic Oncology, Institute of Oncology, Dokuz Eylül University, 35330 İzmir, TurkeyDepartment of Clinical Oncology, Institute of Oncology, Dokuz Eylül University, 35330 İzmir, TurkeyDepartment of Basic Oncology, Institute of Oncology, Dokuz Eylül University, 35330 İzmir, TurkeyDepartment of Basic Oncology, Institute of Oncology, Dokuz Eylül University, 35330 İzmir, TurkeyDepartment of Basic Oncology, Institute of Oncology, Dokuz Eylül University, 35330 İzmir, TurkeyDepartment of Basic Oncology, Institute of Oncology, Dokuz Eylül University, 35330 İzmir, TurkeyDepartment of Basic Oncology, Institute of Oncology, Dokuz Eylül University, 35330 İzmir, TurkeyDepartment of Basic Oncology, Institute of Oncology, Dokuz Eylül University, 35330 İzmir, TurkeyDepartment of Tumor Pathology, Institute of Oncology, Dokuz Eylül University, 35330 İzmir, TurkeyDepartment of Clinical Oncology, Institute of Oncology, Dokuz Eylül University, 35330 İzmir, TurkeyDepartment of Clinical Oncology, Institute of Oncology, Dokuz Eylül University, 35330 İzmir, TurkeyDepartment of Clinical Oncology, Institute of Oncology, Dokuz Eylül University, 35330 İzmir, TurkeyBackground: There is considerable interest in the molecular evaluation of solid tumors in pediatric cases. Although clinical trials are in progress for targeted therapies against neuroblastoma (NB), novel therapeutic strategies are needed for high-risk cases that are resistant to therapy. The aim of the present study was to document the specific gene mutations related to targeted therapy in relapsed or refractory NB patients by using next generation sequencing (NGS). Methods: The study included 57 NB patients from amongst 1965 neuroblastic cases in Turkey who experienced a recurrence after multi-model therapy. The cases were diagnosed, risk-stratified, and treated according to the classification system from the International Neuroblastoma Risk Group. Single nucleotide variations in 60 genes were investigated using the Pillar Onco/Reveal Multicancer v4 panel and Pillar RNA fusion panel on the Illumina Miniseq platform. Results: ERBB2 I655V was the most frequent mutation and was found in 39.65% of cases. Anaplastic Lymphoma Kinase (ALK) mutations (F1174L, R1275Q, and rare mutations in the tyrosine kinase domain) were detected in 29.3% of cases. Fusion mutations in NTRK1, NTRK3, ROS1, RET, FGFR3, ALK and BRAF were observed in 19.6% of cases. Conclusions: This study presents valuable mutation data for relapsed and refractory NB patients. The high frequency of the ERBB2 I655V mutation may allow further exploration of this mutation as a potential therapeutic target. Rare BRAF mutations may also provide opportunities for targeted therapy. The role of ABL1 mutations in NB should also be explored further.https://www.imrpress.com/journal/FBL/28/8/10.31083/j.fbl2808171neuroblastomamutationhigh-throughput nucleotide sequencingtherapyanaplastic lymphoma kinaseerbb-2braf-kiaa1549 fusion proteindna mutational analysis |
| spellingShingle | Tekincan Aktas Deniz Kızmazoglu Safiye Aktas Aylin Erol Efe Serinan Ozde Gokbayrak Sefayi Merve Ozdemir Zekiye Altun Erdener Ozer Emre Cecen Dilek Ince Nur Olgun Unraveling the Mystery: Next Generation Sequencing Sheds Light on Neuroblastoma Pathogenesis and Targeted Therapies Frontiers in Bioscience-Landmark neuroblastoma mutation high-throughput nucleotide sequencing therapy anaplastic lymphoma kinase erbb-2 braf-kiaa1549 fusion protein dna mutational analysis |
| title | Unraveling the Mystery: Next Generation Sequencing Sheds Light on Neuroblastoma Pathogenesis and Targeted Therapies |
| title_full | Unraveling the Mystery: Next Generation Sequencing Sheds Light on Neuroblastoma Pathogenesis and Targeted Therapies |
| title_fullStr | Unraveling the Mystery: Next Generation Sequencing Sheds Light on Neuroblastoma Pathogenesis and Targeted Therapies |
| title_full_unstemmed | Unraveling the Mystery: Next Generation Sequencing Sheds Light on Neuroblastoma Pathogenesis and Targeted Therapies |
| title_short | Unraveling the Mystery: Next Generation Sequencing Sheds Light on Neuroblastoma Pathogenesis and Targeted Therapies |
| title_sort | unraveling the mystery next generation sequencing sheds light on neuroblastoma pathogenesis and targeted therapies |
| topic | neuroblastoma mutation high-throughput nucleotide sequencing therapy anaplastic lymphoma kinase erbb-2 braf-kiaa1549 fusion protein dna mutational analysis |
| url | https://www.imrpress.com/journal/FBL/28/8/10.31083/j.fbl2808171 |
| work_keys_str_mv | AT tekincanaktas unravelingthemysterynextgenerationsequencingshedslightonneuroblastomapathogenesisandtargetedtherapies AT denizkızmazoglu unravelingthemysterynextgenerationsequencingshedslightonneuroblastomapathogenesisandtargetedtherapies AT safiyeaktas unravelingthemysterynextgenerationsequencingshedslightonneuroblastomapathogenesisandtargetedtherapies AT aylinerol unravelingthemysterynextgenerationsequencingshedslightonneuroblastomapathogenesisandtargetedtherapies AT efeserinan unravelingthemysterynextgenerationsequencingshedslightonneuroblastomapathogenesisandtargetedtherapies AT ozdegokbayrak unravelingthemysterynextgenerationsequencingshedslightonneuroblastomapathogenesisandtargetedtherapies AT sefayimerveozdemir unravelingthemysterynextgenerationsequencingshedslightonneuroblastomapathogenesisandtargetedtherapies AT zekiyealtun unravelingthemysterynextgenerationsequencingshedslightonneuroblastomapathogenesisandtargetedtherapies AT erdenerozer unravelingthemysterynextgenerationsequencingshedslightonneuroblastomapathogenesisandtargetedtherapies AT emrececen unravelingthemysterynextgenerationsequencingshedslightonneuroblastomapathogenesisandtargetedtherapies AT dilekince unravelingthemysterynextgenerationsequencingshedslightonneuroblastomapathogenesisandtargetedtherapies AT nurolgun unravelingthemysterynextgenerationsequencingshedslightonneuroblastomapathogenesisandtargetedtherapies |