Data documento
02/05/2024

Título
Establishment and molecular characterization of HCB‑541, a novel and aggressive human cutaneous squamous cell carcinoma cell line

Autor(es)
LAUS, Ana Carolina - GOMES, Izabela Natalia Faria - SILVA, Aline Larissa Virginio da - SILVA, Luciane Sussuchi da - MILAN, Mirella Baroni - TEIXEIRA, Silvia Aparecida - MARTINS, Ana Carolina Baptista Moreno - PEREIRA, Letícia do Nascimento Braga - CARVALHO, Carlos Eduardo Barbosa de - CROVADOR, Camila Souza - PAULA, Flávia Escremin de - NASCIMENTO, Flávia Caroline - FREITAS, Helder Teixeira de - VAZQUEZ, Vinicius de Lima - REIAS, Rui Manuel - OLIVEIRA, Renato José da Silva.

Palavras chave
Cutaneous squamous cell carcinoma - Molecular profile - Cell line establishment - In vivo model

Resumo
Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient. A tumor biopsy was taken from a metastatic cSCC patient, immortalized, and named HCB-541 after several passages. The cytokeratin expression profile, karyotypic alterations, mutational analysis, mRNA and protein differential expression, tumorigenic capacity in xenograft models, and drug sensitivity were analyzed. The HCB-541 cell line showed a doubling time between 20 and 30 h and high tumorigenic capacity in the xenograft mouse model. The HCB-541 cell line showed hypodiploid and hypotetraploidy populations. We found pathogenic mutations in TP53 p.(Arg248Leu), HRAS (Gln61His) and TERT promoter (C228T) and high-level microsatellite instability (MSI-H) in both tumor and cell line. We observed 37 cancer-related genes differentially expressed when compared with HACAT control cells. The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.

Citação
Laus AC, Gomes INF, da Silva ALV, da Silva LS, Milan MB, AparecidaTeixeira S, Martin ACBM, do Nascimento Braga Pereira L, de Carvalho CEB, Crovador CS, de Paula FE, Nascimento FC, de Freitas HT, de Lima Vazquez V, Reis RM, da Silva-Oliveira RJ. Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line. Hum Cell. 2024 Apr 3. doi: 10.1007/s13577-024-01054-1. Epub ahead of print. PMID: 38565739.

Data documento
19/03/2025

Título
Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line.

Autor(es)
Laus AC - Gomes INF - da Silva ALV - da Silva LS - Milan MB - AparecidaTeixeira S - Martin ACBM - do Nascimento Braga Pereira L - de Carvalho CEB - Crovador CS - de Paula FE - Nascimento FC - de Freitas HT - de Lima Vazquez V - Reis RM - da Silva-Oliveira RJ

Palavras chave
Cell line establishment; Cutaneous squamous cell carcinoma; In vivo model; Molecular profile.

Resumo
Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient. A tumor biopsy was taken from a metastatic cSCC patient, immortalized, and named HCB-541 after several passages. The cytokeratin expression profile, karyotypic alterations, mutational analysis, mRNA and protein differential expression, tumorigenic capacity in xenograft models, and drug sensitivity were analyzed. The HCB-541 cell line showed a doubling time between 20 and 30 h and high tumorigenic capacity in the xenograft mouse model. The HCB-541 cell line showed hypodiploid and hypotetraploidy populations. We found pathogenic mutations in TP53 p.(Arg248Leu), HRAS (Gln61His) and TERT promoter (C228T) and high-level microsatellite instability (MSI-H) in both tumor and cell line. We observed 37 cancer-related genes differentially expressed when compared with HACAT control cells. The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.

Citação
Laus AC, Gomes INF, da Silva ALV, da Silva LS, Milan MB, AparecidaTeixeira S, Martin ACBM, do Nascimento Braga Pereira L, de Carvalho CEB, Crovador CS, de Paula FE, Nascimento FC, de Freitas HT, de Lima Vazquez V, Reis RM, da Silva-Oliveira RJ. Hum Cell. 2024 Jul;37(4):1170-1183. doi: 10.1007/s13577-024-01054-1. Epub 2024 Apr 3. PMID: 38565739

Data documento
13/03/2025

Título
Molecular profile of driver genes in lung adenocarcinomas of Brazilian patients who have never smoked: implications for targeted therapies

Autor(es)
Rodrigo de Oliveira Cavagna - Flávia Escremim de Paula - Gustavo Noriz Berardinelli - Murilo Bonatelli - Iara Santana - Eduardo Caetano Albino da Silva - Gustavo Ramos Teixeira - Beatriz Garbe Zaniolo - Flávio Augusto Ferreira da Silva - Carlos Eduardo Baston Silva - Josiane Mourão Dias - Marcela Gondim Borges Guimarães - Camila Pinto Barone - Alexandre Arthur Jacinto - Rachid Eduardo Noleto da Nóbrega Oliveira - José Elias Miziara - Pedro De Marchi - Miguel A. Molina-Vila - Letícia Ferro Leal - Rui Manuel Reis

Palavras chave
lung adenocarcinoma; molecular profile; driver mutations; never smoker; Latin America.

Resumo
Introduction: Lung cancer in never-smoker (LCINS) patients accounts for 20% of lung cancer cases, and its biology remains poorly understood, particularly in genetically admixed populations. We elucidated the molecular profile of driver genes in Brazilian LCINS. Methods: The mutational and gene fusion status of 119 lung adenocarcinomas from self-reported never-smoker patients, was assessed using targeted sequencing (NGS), nCounter, and immunohistochemistry. A panel of 46 ancestry-informative markers determined patients’ genetic ancestry. Results: The most frequently mutated gene was EGFR (49.6%), followed by TP53 (39.5%), ALK (12.6%), ERBB2 (7.6%), KRAS (5.9%), PIK3CA (1.7%), and less than 1% alterations in RET, NTRK1, MET∆ex14, PDGFRA, and BRAF. Except for TP53 and PIK3CA, all other alterations were mutually exclusive. Genetic ancestry analysis revealed a predominance of European (71.1%), and a higher African ancestry was associated with TP53 mutations. Conclusion: Brazilian LCINS exhibited a similar molecular profile to other populations, except the increased ALK and TP53 alterations. Importantly, 73% of these patients have actionable alterations that are suitable for targeted treatments.

Citação
Cavagna RO, Escremim de Paula F, Berardinelli GN, Bonatelli M, Santana I, Albino da Silva EC, Teixeira GR, Zaniolo BG, Mourão Dias J, Ferreira da Silva FA, Baston Silva CE, Guimarães MGB, Barone CP, Jacinto AA, Noleto da Nóbrega Oliveira RE, Miziara JE, De Marchi P, Molina-Vila MA, Leal LF, Reis RM. Oncologist. 2024 Oct 3;29(10):e1419-e1424. doi: 10.1093/oncolo/oyae129. PMID: 38944844