Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic Profiling
| Autor: | Balazs Halmos, James Suh, Jane Liu, Manuel Doria, Jeffrey S. Ross, Sai-Hong Ignatius Ou, K. Cynthia Hsieh, Ranee Mehra, Vincent A. Miller, James A. Knost, Paul A. S. Fishkin, Philip J. Stephens, Garrett M. Frampton, Steven C. Buck, Alexa B. Schrock, Nir Peled, Nagla Abdel Karim, Siraj M. Ali, Jose A. Bufill, Rong Chen, Eduardo Braun, Shuyu D. Li |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Pulmonary and Respiratory Medicine Lung Neoplasms endocrine system diseases medicine.medical_treatment Disease Adenocarcinoma Bioinformatics medicine.disease_cause Proto-Oncogene Mas 03 medical and health sciences Exon 0302 clinical medicine Carcinosarcoma Carcinoma Non-Small-Cell Lung Biomarkers Tumor medicine Humans Prospective Studies Sarcomatoid carcinoma Gene Aged Aged 80 and over Chemotherapy business.industry Gene Expression Profiling Cancer Genomics Immunotherapy Middle Aged Prognosis medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis Mutation Cancer research Female KRAS business Follow-Up Studies |
| Zdroj: | Journal of Thoracic Oncology. 12:932-942 |
| ISSN: | 1556-0864 |
| DOI: | 10.1016/j.jtho.2017.03.005 |
| Popis: | 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.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.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%) (p0.0001) 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.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. |
| Databáze: | OpenAIRE |
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