Browsing by Author "Sánchez, Carolina"
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Publication A germline variant of ring finger protein 43 in an early onset, treatment-resistant metastatic gastric cancer: a case report(2025) García-Bloj, Benjamín; Celis, Santiago Farah; Orellana, Natalia Eva; Glasser, Tomás de Mayo; Sáez, Mauricio A.; Retamal, Ignacio N.; Muñoz-Medel, Matías; Sánchez, Carolina; Pinto, Felipe; Aravena, Paola; San Martín, Cristopher; Sabioncello, Andrea C.; Garrido Villanueva, Marcelo; Sigler Chávez, Fernando; Ríos Leal, Juvenal A.; Manque, Patricio A.; Erpel, José M.; Godoy, Juan A.; Garrido, MarceloBackground: Ring finger protein 43 (RNF43) is an E3 ubiquitin-protein ligase that functions as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination, endocytosis, and subsequent degradation of Frizzled receptors within the Wnt receptor complex. It exerts its effects on both canonical and non-canonical Wnt signaling pathways. Case Description: This case report describes a 49-year-old female patient with a significant family history of cancer and parental consanguinity who was diagnosed with treatment-resistant stage IV gastric adenocarcinoma. Genomic profiling conducted via liquid biopsy identified a missense variant in RNF43 exon 9 (NM_017763.6, c.1948C>T; Arg650Ter) with a high variant allele frequency (VAF) of 49.5%. Confirmation of the R650* variant at the germline level underscores its clinical significance in early onset gastric cancer (GC) pathogenesis. Conclusions: While interpretations of its pathogenicity vary in the ClinVar database, the application of the American College of Medical Genetics (ACMG) criteria suggests its potential involvement in cancer pathogenesis. This report highlights the necessity for further research to elucidate the role and impact of RNF43 in GC progression and develop specific preventive measures for affected families as genetic testing and counseling in high-risk families.Publication Beyond tobacco: genomic disparities in lung cancer between smokers and never-smokers(2024) Garrido, Javiera; Bernal, Yanara; González, Evelin; Blanco, Alejandro; Sepúlveda, Gonzalo; Freire, Matías; Oróstica, Karen; Rivas, Solange; Marcelain, Katherine; Owen, Gareth; Ibañez, Carolina; Corvalan, Alejandro; Garrido, Marcelo; Assar, Rodrigo; Lizana, Rodrigo; Cáceres, Javier; Ampuero, Diego; Ramos, Liliana; Pérez, Paola; Aren, Osvaldo; Chernilo, Sara; Fernández, Cristina; Spencer, María; Flores, Jacqueline; Bernal, Giuliano; Ahumada, Mónica; Rasse, Germán; Sánchez, Carolina; De Amorim, Maria; Bartelli, Thais; Noronha, Diana; Dias, Emmanuel; Freitas, Helano; Armisén, RicardoBackground: Tobacco use is one of the main risk factors for Lung Cancer (LC) development. However, about 10-20% of those diagnosed with the disease are never-smokers. For Non-Small Cell Lung Cancer (NSCLC) there are clear differences in both the clinical presentation and the tumor genomic profiles between smokers and never-smokers. For example, the Lung Adenocarcinoma (LUAD) histological subtype in never-smokers is predominately found in young women of European, North American, and Asian descent. While the clinical presentation and tumor genomic profiles of smokers have been widely examined, never-smokers are usually underrepresented, especially those of a Latin American (LA) background. In this work, we characterize, for the first time, the difference in the genomic profiles between smokers and never-smokers LC patients from Chile. Methods: We conduct a comparison by smoking status in the frequencies of genomic alterations (GAs) including somatic mutations and structural variants (fusions) in a total of 10 clinically relevant genes, including the eight most common actionable genes for LC (EGFR, KRAS, ALK, MET, BRAF, RET, ERBB2, and ROS1) and two established driver genes for malignancies other than LC (PIK3CA and MAP2K1). Study participants were grouped as either smokers (current and former, n = 473) or never-smokers (n = 200) according to self-report tobacco use at enrollment. Results: Our findings indicate a higher overall GA frequency for never-smokers compared to smokers (58 vs. 45.7, p-value < 0.01) with the genes EGFR, KRAS, and PIK3CA displaying the highest prevalence while ERBB2, RET, and ROS1 the lowest. Never-smokers present higher frequencies in seven out of the 10 genes; however, smokers harbor a more complex genomic profile. The clearest differences between groups are seen for EGFR (15.6 vs. 21.5, p-value: < 0.01), PIK3CA (6.8 vs 9.5) and ALK (3.2 vs 7.5) in favor of never-smokers, and KRAS (16.3 vs. 11.5) and MAP2K1 (6.6 vs. 3.5) in favor of smokers. Alterations in these genes are comprised almost exclusively by somatic mutations in EGFR and mainly by fusions in ALK, and only by mutations in PIK3CA, KRAS and MAP2K1. Conclusions: We found clear differences in the genomic landscape by smoking status in LUAD patients from Chile, with potential implications for clinical management in these limited-resource settings.Publication Comprehensive in‑silico molecular analysis of early‑onset gastric cancer identifies novel genes implicated in disease characterization and progression (Review)(2025) Gómez‑Valenzuela, Fernán; Silva, Ian; Retamal, Ignacio N.; García‑Bloj, Benjamín; De Mayo Glasser, Tomás; Muñoz‑Medel, Matías; Gómez, Alex; San Martín, Cristopher; Sánchez, Carolina; Pinto, Felipe; Aravena, Paola; Sabioncello, Andrea C.; Garrido Villanueva, Marcelo; Sigler Chávez, Fernado; Corvalán, Ignacio; Barrios, Henry; Erpel, José M.; Manque, Patricio A.; Godoy, Juan A.; Garrido, MarceloGastric cancer, a prevalent and fatal form of cancer worldwide, is manifested at different age ranges during the lifespan. Approximately one‑third of newly diagnosed gastric cancer cases are early‑onset gastric cancer (EO‑GC), which affects individuals under the age of 50 years. EO‑GC tends to be more aggressive than late‑onset gastric cancer (L‑GC), with a faster and multifocal disease progression. Furthermore, EO‑GC is associated with early metastatic disease. Recent research has underscored the need for a deeper understanding of EO‑GC that promotes therapeutic approaches specific to EO‑GC. The present study determined the main transcrip‑tomic differences between EO‑GC and L‑GC. Transcriptomic expression data from The Cancer Genome Atlas‑Stomach Adenocarcinoma were explored to elucidate whether age is associated with a specific genomic expression pattern and is associated with gastric cancer. Subsequently, a differential gene expression analysis of the EO‑GC vs. L‑GC groups was performed, providing new insights into EO‑GC gene expression characteristics and their association with survival outcomes. Furthermore, the study focused on whether the influence of representative gene expression in EO‑GC cases (KLHL4, MAGEL2, CYP8B1, RNLS, CLDN6, MIOX, PNMA5 and ACTL8 genes) may be associated with its aggressive phenotype and methylation profiles of these patients. In this review, the necessity of incorporating age as a crucial element in understanding the disparities in outcomes for EO‑GC cases in public datasets was discussed. Furthermore, this insight may be useful for targeted early personalized clinical interventions to improve patient prognosis and survival rates in EO‑GC cases.Item Concordance analysis of ALK gene fusion detection methods in patients with Non– Small-Cell Lung Cancer from Chile, Brazil, and Peru(2021-06) Sepúlveda-Hermosilla, Gonzalo; Freire, Matías; Blanco, Alejandro; Cáceres, Javier; Lizana, Rodrigo; Ramos, Liliana; Assar, Rodrigo; Ampuero, Diego; Aren, Osvaldo; Chernilo, Sara; Spencer, María Loreto; Bernal, Giuliano; Flores, Jacqueline; Rasse, Germán; Sánchez, Carolina; Marcelain, Katherine; Rivas, Solange; Pereira Branco, Gabriela; Galli de Amorim, María; Noronha Nunes, Diana; Dias-Neto, Emmanuel; Freitas, Helano C.; Fernández, Cristina; Pérez, Paola; NIRVANA team; Armisén, RicardoAbout 4 to 7 % of the Non-small cell lung cancer patients have ALK rearrangements and specific target therapies improve patients’ outcomes significantly. ALK gene fusions are detected by immunohistochemistry (IHC) or Fluorescent in situ Hybridization (FISH) as gold standards in South America. Next Generation Sequencing (NGS) based assays are a reliable alternative, able to perform simultaneous detection of multiple events from a single sample. We analyzed 4,240 Non-small cell lung cancer samples collected in 37 hospitals from Chile, Brazil, and Peru; where ALK rearrangements were determined as part of their standard of care (SofC) using either IHC or FISH. A subset of 1450 samples was sequenced with the Oncomine Focus Assay (OFA), and the concordance with the SofC tests was measured. An orthogonal analysis was performed using a qPCR EML4-ALK fusion detection kit. ALK fusion prevalence is very similar for Chile (3.67%, N=2142), Brazil (4.05%, N=1013) and Peru (4.59%, N=675). Whereas a comparison between OFA and SofC assays showed similar sensitivity, OFA had significantly higher specificity and higher positive predictive value, which opens new opportunities for a more specific determination of ALK gene rearrangements.