Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic Profiling
Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved..
INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a high-grade NSCLC characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered because of limited and inconsistent molecular characterization.
METHODS: Hybrid capture-based comprehensive genomic profiling was performed on DNA from formalin-fixed paraffin-embedded sections of 15,867 NSCLCs, including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1.11 megabases (Mb) of sequenced DNA.
RESULTS: The median age of the patients with PSC was 67 years (range 32-87), 58% were male, and 78% had stage IV disease. Tumor protein p53 gene (TP53) genomic alterations (GAs) were identified in 74% of cases, which had genomics distinct from TP53 wild-type cases, and 62% featured a GA in KRAS (34%) or one of seven genes currently recommended for testing in the National Comprehensive Cancer Network NSCLC guidelines, including the following: hepatocyte growth factor receptor gene (MET) (13.6%), EGFR (8.8%), BRAF (7.2%), erb-b2 receptor tyrosine kinase 2 gene (HER2) (1.6%), and ret proto-oncogene (RET) (0.8%). MET exon 14 alterations were enriched in PSC (12%) compared with non-PSC NSCLCs (∼3%) (p < 0.0001) and were more prevalent in PSC cases with an adenocarcinoma component. The fraction of PSC with a high TMB (>20 mutations per Mb) was notably higher than in non-PSC NSCLC (20% versus 14%, p = 0.056). Of nine patients with PSC treated with targeted or immunotherapies, three had partial responses and three had stable disease.
CONCLUSION: Potentially targetable GAs in National Comprehensive Cancer Network NSCLC genes (30%) or intermediate or high TMB (43%, >10 mutations per Mb) were identified in most of the PSC cases. Thus, the use of comprehensive genomic profiling in clinical care may provide important treatment options for a historically poorly characterized and difficult to treat disease.
| Errataetall: |
CommentIn: J Thorac Oncol. 2017 Jun;12(6):910-912. - PMID 28532559 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer - 12(2017), 6 vom: 11. Juni, Seite 932-942 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schrock, Alexa B [VerfasserIn] |
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| Links: |
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| Themen: |
BRAF |
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| Anmerkungen: |
Date Completed 14.03.2018 Date Revised 19.04.2022 published: Print-Electronic CommentIn: J Thorac Oncol. 2017 Jun;12(6):910-912. - PMID 28532559 Citation Status MEDLINE |
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| doi: |
10.1016/j.jtho.2017.03.005 |
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NLM270054537 |
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| 245 | 1 | 0 | |a Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic Profiling |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 14.03.2018 | ||
| 500 | |a Date Revised 19.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: J Thorac Oncol. 2017 Jun;12(6):910-912. - PMID 28532559 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a high-grade NSCLC characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered because of limited and inconsistent molecular characterization | ||
| 520 | |a METHODS: Hybrid capture-based comprehensive genomic profiling was performed on DNA from formalin-fixed paraffin-embedded sections of 15,867 NSCLCs, including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1.11 megabases (Mb) of sequenced DNA | ||
| 520 | |a RESULTS: The median age of the patients with PSC was 67 years (range 32-87), 58% were male, and 78% had stage IV disease. Tumor protein p53 gene (TP53) genomic alterations (GAs) were identified in 74% of cases, which had genomics distinct from TP53 wild-type cases, and 62% featured a GA in KRAS (34%) or one of seven genes currently recommended for testing in the National Comprehensive Cancer Network NSCLC guidelines, including the following: hepatocyte growth factor receptor gene (MET) (13.6%), EGFR (8.8%), BRAF (7.2%), erb-b2 receptor tyrosine kinase 2 gene (HER2) (1.6%), and ret proto-oncogene (RET) (0.8%). MET exon 14 alterations were enriched in PSC (12%) compared with non-PSC NSCLCs (∼3%) (p < 0.0001) and were more prevalent in PSC cases with an adenocarcinoma component. The fraction of PSC with a high TMB (>20 mutations per Mb) was notably higher than in non-PSC NSCLC (20% versus 14%, p = 0.056). Of nine patients with PSC treated with targeted or immunotherapies, three had partial responses and three had stable disease | ||
| 520 | |a CONCLUSION: Potentially targetable GAs in National Comprehensive Cancer Network NSCLC genes (30%) or intermediate or high TMB (43%, >10 mutations per Mb) were identified in most of the PSC cases. Thus, the use of comprehensive genomic profiling in clinical care may provide important treatment options for a historically poorly characterized and difficult to treat disease | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Genomic profiling | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Lung sarcomatoid | |
| 650 | 4 | |a MET exon 14 | |
| 650 | 4 | |a Tumor mutational burden | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a MAS1 protein, human |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Mas |2 NLM | |
| 700 | 1 | |a Li, Shuyu D |e verfasserin |4 aut | |
| 700 | 1 | |a Frampton, Garrett M |e verfasserin |4 aut | |
| 700 | 1 | |a Suh, James |e verfasserin |4 aut | |
| 700 | 1 | |a Braun, Eduardo |e verfasserin |4 aut | |
| 700 | 1 | |a Mehra, Ranee |e verfasserin |4 aut | |
| 700 | 1 | |a Buck, Steven C |e verfasserin |4 aut | |
| 700 | 1 | |a Bufill, Jose A |e verfasserin |4 aut | |
| 700 | 1 | |a Peled, Nir |e verfasserin |4 aut | |
| 700 | 1 | |a Karim, Nagla Abdel |e verfasserin |4 aut | |
| 700 | 1 | |a Hsieh, K Cynthia |e verfasserin |4 aut | |
| 700 | 1 | |a Doria, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Knost, James |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Rong |e verfasserin |4 aut | |
| 700 | 1 | |a Ou, Sai-Hong Ignatius |e verfasserin |4 aut | |
| 700 | 1 | |a Ross, Jeffrey S |e verfasserin |4 aut | |
| 700 | 1 | |a Stephens, Philip J |e verfasserin |4 aut | |
| 700 | 1 | |a Fishkin, Paul |e verfasserin |4 aut | |
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| 700 | 1 | |a Halmos, Balazs |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jane J |e verfasserin |4 aut | |
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