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Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma
BACKGROUND: Histiocytic and dendritic cell neoplasms are a diverse group of tumors arising from monocytic or dendritic cell lineage. Whereas the genomic features for Langerhans cell histiocytosis and Erdheim‐Chester disease have been well described, other less common and often aggressive tumors in t...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265357/ https://www.ncbi.nlm.nih.gov/pubmed/33904632 http://dx.doi.org/10.1002/onco.13801 |
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author | Massoth, Lucas R. Hung, Yin P. Ferry, Judith A. Hasserjian, Robert P. Nardi, Valentina Nielsen, G. Petur Sadigh, Sam Venkataraman, Vinayak Selig, Martin Friedmann, Alison M. Samore, Wesley Killian, Jonathan Keith Milante, Riza Giessinger, Joseph Foley‐Peres, Kathleen Marcus, Chelsea Severson, Eric Duncan, Daniel Sivakumar, Smruthy Ross, Jeffrey S. Desphande, Vikram Ramkissoon, Shakti H. Vergilio, Jo‐Anne Louissaint, Abner Zukerberg, Lawrence R. Williams, Erik A. |
author_facet | Massoth, Lucas R. Hung, Yin P. Ferry, Judith A. Hasserjian, Robert P. Nardi, Valentina Nielsen, G. Petur Sadigh, Sam Venkataraman, Vinayak Selig, Martin Friedmann, Alison M. Samore, Wesley Killian, Jonathan Keith Milante, Riza Giessinger, Joseph Foley‐Peres, Kathleen Marcus, Chelsea Severson, Eric Duncan, Daniel Sivakumar, Smruthy Ross, Jeffrey S. Desphande, Vikram Ramkissoon, Shakti H. Vergilio, Jo‐Anne Louissaint, Abner Zukerberg, Lawrence R. Williams, Erik A. |
author_sort | Massoth, Lucas R. |
collection | PubMed |
description | BACKGROUND: Histiocytic and dendritic cell neoplasms are a diverse group of tumors arising from monocytic or dendritic cell lineage. Whereas the genomic features for Langerhans cell histiocytosis and Erdheim‐Chester disease have been well described, other less common and often aggressive tumors in this broad category remain poorly characterized, and comparison studies across the World Health Organization diagnostic categories are lacking. METHODS: Tumor samples from a total of 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs), underwent hybridization capture with analysis of up to 406 cancer‐related genes. RESULTS: Among the entire cohort of 102 patients, CDKN2A mutations were most frequent across subtypes and made up 32% of cases, followed by TP53 mutations (22%). Mitogen‐activated protein kinase (MAPK) pathway mutations were present and enriched among the malignant histiocytosis (M) group (HS, IDCS, and LCS) but absent in FDCS (72% vs. 0%; p < .0001). In contrast, NF‐κB pathway mutations were frequent in FDCSs but rare in M group histiocytoses (61% vs. 12%; p < .0001). Tumor mutational burden was significantly higher in M group histiocytoses as compared with FDCSs (median 4.0/Mb vs. 2.4/Mb; p = .012). We also describe a pediatric patient with recurrent secondary histiocytic sarcoma treated with targeted therapy and interrogated by molecular analysis to identify mechanisms of therapeutic resistance. CONCLUSION: A total of 42 patient tumors (41%) harbored pathogenic mutations that were potentially targetable by approved and/or investigative therapies. Our findings highlight the potential value of molecular testing to enable precise tumor classification, identify candidate oncogenic drivers, and define personalized therapeutic options for patients with these aggressive tumors. IMPLICATIONS FOR PRACTICE: This study presents comprehensive genomic profiling results on 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs). MAPK pathway mutations were present and enriched among the malignant histiocytosis (M) group (HS, IDCS, and LCS) but absent in FDCSs. In contrast, NF‐κB pathway mutations were frequent in FDCSs but rare in M group histiocytosis. A total of 42 patient tumors (41%) harbored pathogenic mutations that were potentially targetable by approved and/or investigative therapies. |
format | Online Article Text |
id | pubmed-8265357 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82653572021-07-13 Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma Massoth, Lucas R. Hung, Yin P. Ferry, Judith A. Hasserjian, Robert P. Nardi, Valentina Nielsen, G. Petur Sadigh, Sam Venkataraman, Vinayak Selig, Martin Friedmann, Alison M. Samore, Wesley Killian, Jonathan Keith Milante, Riza Giessinger, Joseph Foley‐Peres, Kathleen Marcus, Chelsea Severson, Eric Duncan, Daniel Sivakumar, Smruthy Ross, Jeffrey S. Desphande, Vikram Ramkissoon, Shakti H. Vergilio, Jo‐Anne Louissaint, Abner Zukerberg, Lawrence R. Williams, Erik A. Oncologist Sarcomas BACKGROUND: Histiocytic and dendritic cell neoplasms are a diverse group of tumors arising from monocytic or dendritic cell lineage. Whereas the genomic features for Langerhans cell histiocytosis and Erdheim‐Chester disease have been well described, other less common and often aggressive tumors in this broad category remain poorly characterized, and comparison studies across the World Health Organization diagnostic categories are lacking. METHODS: Tumor samples from a total of 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs), underwent hybridization capture with analysis of up to 406 cancer‐related genes. RESULTS: Among the entire cohort of 102 patients, CDKN2A mutations were most frequent across subtypes and made up 32% of cases, followed by TP53 mutations (22%). Mitogen‐activated protein kinase (MAPK) pathway mutations were present and enriched among the malignant histiocytosis (M) group (HS, IDCS, and LCS) but absent in FDCS (72% vs. 0%; p < .0001). In contrast, NF‐κB pathway mutations were frequent in FDCSs but rare in M group histiocytoses (61% vs. 12%; p < .0001). Tumor mutational burden was significantly higher in M group histiocytoses as compared with FDCSs (median 4.0/Mb vs. 2.4/Mb; p = .012). We also describe a pediatric patient with recurrent secondary histiocytic sarcoma treated with targeted therapy and interrogated by molecular analysis to identify mechanisms of therapeutic resistance. CONCLUSION: A total of 42 patient tumors (41%) harbored pathogenic mutations that were potentially targetable by approved and/or investigative therapies. Our findings highlight the potential value of molecular testing to enable precise tumor classification, identify candidate oncogenic drivers, and define personalized therapeutic options for patients with these aggressive tumors. IMPLICATIONS FOR PRACTICE: This study presents comprehensive genomic profiling results on 102 patient cases within four major subtypes of malignant histiocytic and dendritic cell neoplasms, including 44 follicular dendritic cell sarcomas (FDCSs), 41 histiocytic sarcomas (HSs), 7 interdigitating dendritic cell sarcomas (IDCSs), and 10 Langerhans cell sarcomas (LCSs). MAPK pathway mutations were present and enriched among the malignant histiocytosis (M) group (HS, IDCS, and LCS) but absent in FDCSs. In contrast, NF‐κB pathway mutations were frequent in FDCSs but rare in M group histiocytosis. A total of 42 patient tumors (41%) harbored pathogenic mutations that were potentially targetable by approved and/or investigative therapies. John Wiley & Sons, Inc. 2021-05-06 2021-07 /pmc/articles/PMC8265357/ /pubmed/33904632 http://dx.doi.org/10.1002/onco.13801 Text en © 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Sarcomas Massoth, Lucas R. Hung, Yin P. Ferry, Judith A. Hasserjian, Robert P. Nardi, Valentina Nielsen, G. Petur Sadigh, Sam Venkataraman, Vinayak Selig, Martin Friedmann, Alison M. Samore, Wesley Killian, Jonathan Keith Milante, Riza Giessinger, Joseph Foley‐Peres, Kathleen Marcus, Chelsea Severson, Eric Duncan, Daniel Sivakumar, Smruthy Ross, Jeffrey S. Desphande, Vikram Ramkissoon, Shakti H. Vergilio, Jo‐Anne Louissaint, Abner Zukerberg, Lawrence R. Williams, Erik A. Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma |
title | Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma |
title_full | Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma |
title_fullStr | Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma |
title_full_unstemmed | Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma |
title_short | Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma |
title_sort | histiocytic and dendritic cell sarcomas of hematopoietic origin share targetable genomic alterations distinct from follicular dendritic cell sarcoma |
topic | Sarcomas |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265357/ https://www.ncbi.nlm.nih.gov/pubmed/33904632 http://dx.doi.org/10.1002/onco.13801 |
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