Andrés F Cardona1,2, Alejandro Ruiz-Patiño2,3, Oscar Arrieta4, Luisa Ricaurte2, Zyanya Lucia Zatarain-Barrón4, July Rodriguez2,3, Jenny Avila2,3, Leonardo Rojas1,3,5, Gonzalo Recondo6, Feliciano Barron4, Pilar Archila2, Carolina Sotelo2,3, Melissa Bravo2, Nataly Zamudio2, Luis Corrales7, Claudio Martín8, Christian Rolfo9, Lucia Viola10, Hernán Carranza1,2,3, Carlos Vargas1,2,3, Jorge Otero1,2,3, Maritza Bermudez2,3, Tatiana Gamez2,3, Luis Eduardo Pino11, Rafael Rosell12. 1. Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia. 2. Department of Medical Oncology, Foundation for Clinical and Applied Cancer Research - FICMAC, Bogotá, Colombia. 3. Molecular Oncology and Biology Systems Research Group (Fox-G), Universidad el Bosque, Bogotá, Colombia. 4. Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, México. 5. Oncology Department, Clínica Colsanitas, Bogotá, Colombia. 6. Thoracic Oncology Section, Centro de Educación Médica e Investigaciones Clínicas - CEMIC, Buenos Aires, Argentina. 7. Oncology Department, Hospital San Juan de Dios, San José Costa Rica, Costa Rica. 8. Medical Oncology Group, Fleming Institute, Buenos Aires, Argentina. 9. Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, United States. 10. Thoracic Oncology Unit, Fundación Neumológica Colombiana, Bogotá, Colombia. 11. Department of Medical Oncology, Fundación Santa Fé de Bogotá, Bogotá, Colombia. 12. Department of Medical Oncology, Catalan Institute of Oncology, Barcelona, Spain.
Abstract
BACKGROUND: Lung cancer is a public health problem, and squamous cell carcinoma (SCC) is the second most prevalent subtype of this neoplasm. Compared to other subtypes, including adenocarcinoma, SCC is less well understood in terms of molecular pathogenesis, limiting therapeutic options among targeted agents approved for other disease subgroups. In this study, we sought to characterize the SCC genomic profile using a validated Next Generation Sequencing (NGS) platform. METHODS: The comprehensive NGS assay (TruSight Tumor 170) was used in order to target the full coding regions of 170 cancer-related genes on SCC samples. PD-L1 expression in tumor cells (TCs) was assessed using clone 22C3 (Dako). Clinical outcomes were correlated with molecular profile, including progression free survival (PFS), overall response rate (ORR), and overall survival (OS). RESULTS: A total of 26 samples were included, median age was 67 years (r, 33-83) and 53.8% were men. Tobacco consumption was identified in all subjects (mean 34-year package). For first-line treatment 80.8% of patients received cisplatin or carboplatin plus gemcitabine. In terms of molecular profile, we identified a high prevalence of inactivating mutations in TP53 (61.5%), PIK3CA (34.6%), MLL2 (34.6%), KEAP1 (38.4%), and NOTCH1 (26.9%). PD-L1 expression ranged from negative, 1, 2-49, and ≥50% in 23.1, 38.5, 26.9, and 11.5%, respectively. Interestingly, the genetic alterations did not have an effect in PFS, OS or ORR in this study. However, PDL1 expression was higher among those who had mutations in TP53 (p = 0.037) and greater expression of PDL1 was related to PIK3CA alterations (p = 0.05). CONCLUSIONS: The genomic profile of SCC encompasses important genes including TP53, PIK3CA and KEAP1. TP53 mutations could be associated with PDL1 expression, generating hypothesis regarding specific treatment options.
BACKGROUND: Lung cancer is a public health problem, and squamous cell carcinoma (SCC) is the second most prevalent subtype of this neoplasm. Compared to other subtypes, including adenocarcinoma, SCC is less well understood in terms of molecular pathogenesis, limiting therapeutic options among targeted agents approved for other disease subgroups. In this study, we sought to characterize the SCC genomic profile using a validated Next Generation Sequencing (NGS) platform. METHODS: The comprehensive NGS assay (TruSight Tumor 170) was used in order to target the full coding regions of 170 cancer-related genes on SCC samples. PD-L1 expression in tumor cells (TCs) was assessed using clone 22C3 (Dako). Clinical outcomes were correlated with molecular profile, including progression free survival (PFS), overall response rate (ORR), and overall survival (OS). RESULTS: A total of 26 samples were included, median age was 67 years (r, 33-83) and 53.8% were men. Tobacco consumption was identified in all subjects (mean 34-year package). For first-line treatment 80.8% of patients received cisplatin or carboplatin plus gemcitabine. In terms of molecular profile, we identified a high prevalence of inactivating mutations in TP53 (61.5%), PIK3CA (34.6%), MLL2 (34.6%), KEAP1 (38.4%), and NOTCH1 (26.9%). PD-L1 expression ranged from negative, 1, 2-49, and ≥50% in 23.1, 38.5, 26.9, and 11.5%, respectively. Interestingly, the genetic alterations did not have an effect in PFS, OS or ORR in this study. However, PDL1 expression was higher among those who had mutations in TP53 (p = 0.037) and greater expression of PDL1 was related to PIK3CA alterations (p = 0.05). CONCLUSIONS: The genomic profile of SCC encompasses important genes including TP53, PIK3CA and KEAP1. TP53 mutations could be associated with PDL1 expression, generating hypothesis regarding specific treatment options.
Authors: William Lee; Zhaoshi Jiang; Jinfeng Liu; Peter M Haverty; Yinghui Guan; Jeremy Stinson; Peng Yue; Yan Zhang; Krishna P Pant; Deepali Bhatt; Connie Ha; Stephanie Johnson; Michael I Kennemer; Sankar Mohan; Igor Nazarenko; Colin Watanabe; Andrew B Sparks; David S Shames; Robert Gentleman; Frederic J de Sauvage; Howard Stern; Ajay Pandita; Dennis G Ballinger; Radoje Drmanac; Zora Modrusan; Somasekar Seshagiri; Zemin Zhang Journal: Nature Date: 2010-05-27 Impact factor: 49.962
Authors: Oscar Arrieta; Andrés F Cardona; Claudio Martín; Luis Más-López; Luis Corrales-Rodríguez; Guillermo Bramuglia; Omar Castillo-Fernandez; Matthew Meyerson; Eduardo Amieva-Rivera; Alma Delia Campos-Parra; Hernán Carranza; Juan Carlos Gómez de la Torre; Yanina Powazniak; Fernando Aldaco-Sarvide; Carlos Vargas; Mariana Trigo; Manuel Magallanes-Maciel; Jorge Otero; Roberto Sánchez-Reyes; Mauricio Cuello Journal: J Thorac Oncol Date: 2015-05 Impact factor: 15.609
Authors: Edward B Garon; Naiyer A Rizvi; Rina Hui; Natasha Leighl; Ani S Balmanoukian; Joseph Paul Eder; Amita Patnaik; Charu Aggarwal; Matthew Gubens; Leora Horn; Enric Carcereny; Myung-Ju Ahn; Enriqueta Felip; Jong-Seok Lee; Matthew D Hellmann; Omid Hamid; Jonathan W Goldman; Jean-Charles Soria; Marisa Dolled-Filhart; Ruth Z Rutledge; Jin Zhang; Jared K Lunceford; Reshma Rangwala; Gregory M Lubiniecki; Charlotte Roach; Kenneth Emancipator; Leena Gandhi Journal: N Engl J Med Date: 2015-04-19 Impact factor: 91.245