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| Natura: | Artículo Open Access |
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Wiley
2024
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| Accesso online: | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6260 |
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| author | Natálie Klubíčková Josephine K Dermawan Elaheh Mosaieby Petr Martínek Tomáš Vaněček Veronika Hájková Nikola Ptáková Petr Grossmann Petr Šteiner Marián Švajdler Zdeněk Kinkor Květoslava Michalová Peter Szepe Lukáš Plank Stanislava Hederová Alexandra Kolenová Neofit Juriev Spasov Kemal Kosemehmetoglu Leo Pažanin Zuzana Špůrková Martin Baník Luděk Baumruk Anders Meyer Antonina Kalmykova Olena Koshyk Michal Michal Michael Michal |
| author_facet | Natálie Klubíčková Josephine K Dermawan Elaheh Mosaieby Petr Martínek Tomáš Vaněček Veronika Hájková Nikola Ptáková Petr Grossmann Petr Šteiner Marián Švajdler Zdeněk Kinkor Květoslava Michalová Peter Szepe Lukáš Plank Stanislava Hederová Alexandra Kolenová Neofit Juriev Spasov Kemal Kosemehmetoglu Leo Pažanin Zuzana Špůrková Martin Baník Luděk Baumruk Anders Meyer Antonina Kalmykova Olena Koshyk Michal Michal Michael Michal Natálie Klubíčková Josephine K Dermawan Elaheh Mosaieby Petr Martínek Tomáš Vaněček Veronika Hájková Nikola Ptáková Petr Grossmann Petr Šteiner Marián Švajdler Zdeněk Kinkor Květoslava Michalová Peter Szepe Lukáš Plank Stanislava Hederová Alexandra Kolenová Neofit Juriev Spasov Kemal Kosemehmetoglu Leo Pažanin Zuzana Špůrková Martin Baník Luděk Baumruk Anders Meyer Antonina Kalmykova Olena Koshyk Michal Michal Michael Michal |
| collection | Wiley Open Access |
| contents | Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with NTRK and other kinase gene aberrations Natálie Klubíčková Josephine K Dermawan Elaheh Mosaieby Petr Martínek Tomáš Vaněček Veronika Hájková Nikola Ptáková Petr Grossmann Petr Šteiner Marián Švajdler Zdeněk Kinkor Květoslava Michalová Peter Szepe Lukáš Plank Stanislava Hederová Alexandra Kolenová Neofit Juriev Spasov Kemal Kosemehmetoglu Leo Pažanin Zuzana Špůrková Martin Baník Luděk Baumruk Anders Meyer Antonina Kalmykova Olena Koshyk Michal Michal Michael Michal The Journal of Pathology Abstract Alterations in kinase genes such as NTRK1/2/3 , RET , and BRAF underlie infantile fibrosarcoma (IFS), the emerging entity ‘ NTRK ‐rearranged spindle cell neoplasms’ included in the latest WHO classification, and a growing set of tumors with overlapping clinical and pathological features. In this study, we conducted a comprehensive clinicopathological and molecular analysis of 22 cases of IFS and other kinase gene‐altered spindle cell neoplasms affecting both pediatric and adult patients. Follow‐up periods for 16 patients ranged in length from 10 to 130 months (mean 38 months). Six patients were treated with targeted therapy, achieving a partial or complete response in five cases. Overall, three cases recurred and one metastasized. Eight patients were free of disease, five were alive with disease, and two patients died. All cases showed previously reported morphological patterns. Based on the cellularity and level of atypia, cases were divided into three morphological grade groups. S100 protein and CD34 were at least focally positive in 12/22 and 14/22 cases, respectively. Novel PWWP2A::RET , NUMA1::RET , ITSN1::RAF1 , and CAPZA2::MET fusions, which we report herein in mesenchymal tumors for the first time, were detected by RNA sequencing. Additionally, the first uterine case with BRAF and EGFR mutations and CD34 and S100 co‐expression is described. DNA sequencing performed in 13 cases uncovered very rare additional genetic aberrations. The CNV profiles showed that high‐grade tumors demonstrate a significantly higher percentage of copy number gains and losses across the genome compared with low‐ and intermediate‐grade tumors. Unsupervised clustering of the tumors’ methylation profiles revealed that in 8/9 cases, the methylation profiles clustered with the IFS methylation class, irrespective of their clinicopathological or molecular features. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6260 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| doi_str_mv | 10.1002/path.6260 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_path_6260 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with NTRK and other kinase gene aberrations Natálie Klubíčková Josephine K Dermawan Elaheh Mosaieby Petr Martínek Tomáš Vaněček Veronika Hájková Nikola Ptáková Petr Grossmann Petr Šteiner Marián Švajdler Zdeněk Kinkor Květoslava Michalová Peter Szepe Lukáš Plank Stanislava Hederová Alexandra Kolenová Neofit Juriev Spasov Kemal Kosemehmetoglu Leo Pažanin Zuzana Špůrková Martin Baník Luděk Baumruk Anders Meyer Antonina Kalmykova Olena Koshyk Michal Michal Michael Michal The Journal of Pathology Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with NTRK and other kinase gene aberrations Natálie Klubíčková Josephine K Dermawan Elaheh Mosaieby Petr Martínek Tomáš Vaněček Veronika Hájková Nikola Ptáková Petr Grossmann Petr Šteiner Marián Švajdler Zdeněk Kinkor Květoslava Michalová Peter Szepe Lukáš Plank Stanislava Hederová Alexandra Kolenová Neofit Juriev Spasov Kemal Kosemehmetoglu Leo Pažanin Zuzana Špůrková Martin Baník Luděk Baumruk Anders Meyer Antonina Kalmykova Olena Koshyk Michal Michal Michael Michal The Journal of Pathology Abstract Alterations in kinase genes such as NTRK1/2/3 , RET , and BRAF underlie infantile fibrosarcoma (IFS), the emerging entity ‘ NTRK ‐rearranged spindle cell neoplasms’ included in the latest WHO classification, and a growing set of tumors with overlapping clinical and pathological features. In this study, we conducted a comprehensive clinicopathological and molecular analysis of 22 cases of IFS and other kinase gene‐altered spindle cell neoplasms affecting both pediatric and adult patients. Follow‐up periods for 16 patients ranged in length from 10 to 130 months (mean 38 months). Six patients were treated with targeted therapy, achieving a partial or complete response in five cases. Overall, three cases recurred and one metastasized. Eight patients were free of disease, five were alive with disease, and two patients died. All cases showed previously reported morphological patterns. Based on the cellularity and level of atypia, cases were divided into three morphological grade groups. S100 protein and CD34 were at least focally positive in 12/22 and 14/22 cases, respectively. Novel PWWP2A::RET , NUMA1::RET , ITSN1::RAF1 , and CAPZA2::MET fusions, which we report herein in mesenchymal tumors for the first time, were detected by RNA sequencing. Additionally, the first uterine case with BRAF and EGFR mutations and CD34 and S100 co‐expression is described. DNA sequencing performed in 13 cases uncovered very rare additional genetic aberrations. The CNV profiles showed that high‐grade tumors demonstrate a significantly higher percentage of copy number gains and losses across the genome compared with low‐ and intermediate‐grade tumors. Unsupervised clustering of the tumors’ methylation profiles revealed that in 8/9 cases, the methylation profiles clustered with the IFS methylation class, irrespective of their clinicopathological or molecular features. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6260 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| title | Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with NTRK and other kinase gene aberrations |
| topic | The Journal of Pathology |
| url | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6260 |