Genotyping Squamous Cell Lung Carcinoma in Colombia (Geno1.1-CLICaP)

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 ap...

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Published in:Frontiers in oncology Vol. 10; p. 588932
Main Authors: Cardona, Andrés F, Ruiz-Patiño, Alejandro, Arrieta, Oscar, Ricaurte, Luisa, Zatarain-Barrón, Zyanya Lucia, Rodriguez, July, Avila, Jenny, Rojas, Leonardo, Recondo, Gonzalo, Barron, Feliciano, Archila, Pilar, Sotelo, Carolina, Bravo, Melissa, Zamudio, Nataly, Corrales, Luis, Martín, Claudio, Rolfo, Christian, Viola, Lucia, Carranza, Hernán, Vargas, Carlos, Otero, Jorge, Bermudez, Maritza, Gamez, Tatiana, Pino, Luis Eduardo, Rosell, Rafael
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 15-12-2020
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Summary: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. The comprehensive NGS assay ( ) 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). 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). 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.
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Edited by: Humam Kadara, University of Texas MD Anderson Cancer Center, United States
Reviewed by: Marzia Del Re, University of Pisa, Italy; Antonio Araujo, University Hospital Center of Porto, Portugal
These authors have contributed equally to this work
This article was submitted to Thoracic Oncology, a section of the journal Frontiers in Oncology
Latin American Consortium for the Investigation of Lung Cancer
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2020.588932