ARMISEN YAÑEZ, RICARDO AMADO

Preferred name
ARMISEN YAÑEZ, RICARDO AMADO
Main Affiliation
Email
rarmisen@udd.cl
ORCID
0000-0003-2567-0521
Scopus Author ID
22956957700
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    NTRK genomic alterations in Latin-American cancer patients.
    (2021)
    CARVAJAL HAUSDORF, DANIEL EDUARDO  
    ;
    Claudio Salas
    ;
    Katherine Marcelain
    ;
    Francisco Perez
    ;
    Evelin Feliu
    <jats:p> e15088 </jats:p><jats:p> Background: The neurotrophic receptor tyrosine kinase genes NTRK1-3 encode the tropomyosin receptor kinase proteins TRKA, TRKB, and TRKC, respectively. TRK fusions lead to overexpression of the chimeric protein, resulting in constitutively active, ligand-independent downstream signaling. NTRKs act as oncogenes, they can be targeted, and it is estimated that they are present in up to 0.3% of tumors. The incidence of actionable alterations in these genes is currently unknown in Latin-American patients. We investigated the presence of NTRK1-3 mutations/rearrangements in 3 independent patient series from several tertiary hospitals from Chile, Brazil and Peru. Methods: 1795 FFPE tumor samples from multiple institutions divided in 3 series were analyzed using 2 NGS panels: Oncomine Focus Assay (OFA; 52 genes) and Oncomine Comprehensive Assay (OCA; 161 genes. Data on NTRK1-3 SNVs, indels, CNVs and fusions was obtained. Bioinformatic workflows were used to study the biologic significance of these alterations. Results: Using OCA (series 1-2), 31 somatic variants were found in gastric, CRC, gallbladder, lung and pancreatic cases out of 300 patients. From these, 13 were located in the tyrosine kinase domain. Using OFA, no NTRK alteration were detected (series 3, 1495 NSCLC cases). Conclusions: NTRK alterations are rare events in Latin-American cancer patients. In 3 series including 1,795 patients, 31 somatic variants were detected. No NTRK fusions or CNVs were identified. The presence of NTRK mutations in the tyrosine kinase domain warrants further research into their potential to benefit from FDA/EMA-approved targeted therapies. [Table: see text] </jats:p>
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    Increase in ADAR1p110 activates the canonical Wnt signaling pathway associated with aggressive phenotype in triple negative breast cancer cells
    (2022)
    Fernanda Morales
    ;
    Paola Pérez
    ;
    Julio C. Tapia
    ;
    Lorena Lobos-González
    ;
    José Manuel Herranz
      2Scopus© Citations 12
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    Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer
    (MDPI AG, 2025-04-03)
    María José Maturana
    ;
    Oslando Padilla
    ;
    Pablo M. Santoro
    ;
    Maria Alejandra Alarcón
    ;
    Wilda Olivares
    Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia/low-grade dysplasia [GIM/LGD]), 21 with high-grade dysplasia/early GC [HGD/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies/mL) was higher than that of the HD controls (139.00 copies/mL) (p &lt; 0.0001). After dividing this cohort into training–validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683–0.845) in the training group. This resulted in a cut-off value of 87.37 copies/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted a sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM/LGD, HGD/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11–3.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53–9.93, p = 0.004) for the risk of developing GIM/LGD and HGD/eGC, respectively. The combined methylated RPRM cfDNA and PG-I/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response.
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    Advances in machine learning for tumour classification in cancer of unknown primary: A mini-review
    (2025)
    Karen Oróstica  
    ;
    Felipe Mardones
    ;
    Yanara A. Bernal
    ;
    Samuel Molina
    ;
    Marcos Orchard
    Scopus© Citations 3  8
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    Transcription-Coupled Repair Promotes the Retention of Mutations in Coding Regions During Replication Stress
    (MDPI AG, 2026-01-23)
    Evelyn Zambrano
    ;
    Cristopher Fierro
    ;
    Fernanda Morales
    ;
    Marcia Manterola
    ;
    Arnaldo Marin
    Replication stress (RS) is a primary driver of genomic instability in cancer, yet the contribution of transcription-coupled repair (TC-NER) to this process remains unclear. Here, we investigate how the TC-NER factor ERCC6 (CSB) shapes mutational landscapes under RS. We found that ERCC6 deficiency biases early damage signaling toward a 53BP1-mediated response, ultimately leading to senescence. Conversely, ERCC6-proficient cells prioritize survival and proliferative recovery but at the expense of distinct genomic alterations. Whole-exome sequencing reveals that ERCC6 proficiency is associated with the retention of stress-induced mutations specifically within coding regions of transcriptionally active loci, whereas ERCC6-deficient cells accumulate variants primarily in intergenic regions. These findings suggest that while ERCC6 safeguards transcriptional continuity during RS, its activity is associated with a biased retention of stress-induced mutations within coding regions in the surviving cell population. These findings reveal a previously unrecognized link between transcription-coupled repair and mutation distribution in human cells, linking TC-NER to context-dependent somatic evolution and tumor heterogeneity.
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    Abstract 6440: Effects of cumulative tobacco exposure on lung cancer genomic profiles in Latin Americans
    (American Association for Cancer Research (AACR), 2026-04-03)
    Javiera Garrido
    ;
    Evelin González
    ;
    Alejandro Blanco
    ;
    Gonzalo Sepúlveda-Hermosilla
    ;
    Matias Freire
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Motivation:</jats:title> <jats:p>Tobacco exposure is a major determinant of tumor genomic landscapes in non-small cell lung cancer (NSCLC). Two of the most clinically relevant actionable genes in lung cancer, EGFR and KRAS, show opposite patterns, with smokers exhibiting a higher prevalence of alterations in KRAS and never-smokers in EGFR. Yet, the dynamic and evolution of genomic changes as a function of cumulative tobacco exposure has received limited attention. Here, we examine how tumor genomic profiles vary according to smoking intensity, duration, and time since cessation (TSC). Our study focuses on an underrepresented population of Latin American patients, where additional research is needed to better characterize tumor heterogeneity.</jats:p> </jats:sec> <jats:sec> <jats:title>Methodology:</jats:title> <jats:p>The population was obtained from the protocol Characterization and Validation of Molecular Diagnostic Technologies for Lung Cancer Patients from Chile, Brazil, and Peru. Participant recruitment was between July 2015 and October 2018 across 37 different centers. Primary or metastatic NSCLC specimens were analyzed, and genomic profiles were generated with the Oncomine Focus Assay (OFA). A total of 1,864 participants yielded QC-approved genomic profiles. Covariates of interest were assessed at enrollment. Cumulative tobacco exposure, including smoking intensity (cigarettes per day), duration, and TSC, was quantified using the Comprehensive Smoking Index (CSI). In addition, smoking status (current vs. never) was recoded as a function of TSC in order to identify the time period during which major genomic alterations (GA) are most likely to occur. Descriptive statistics, generalized linear models, and generalized additive models were used to evaluate the association between CSI and the prevalence of GA across genes. All models were adjusted for potential confounders, including country, age, sex, NSCLC subtype, cancer stage and history of cancer.</jats:p> </jats:sec> <jats:sec> <jats:title>Results and Conclusions:</jats:title> <jats:p>A total of 1100 patients had complete genomic and tobacco exposure information. Among current smokers, median smoking intensity and duration were 20 cigarettes per day and 48 years, respectively, compared with 30 cigarettes per day and 47 years among former smokers. Ninety percent of former smokers had ceased tobacco use at least 10 years prior to diagnosis, with a median TSC of 1 year. CSI analysis identified 14 genes significantly associated with genomic alteration status, including EGFR, PIK3CA, ALK, MTOR, ERBB3, and RET. Higher CSI values (4th quartile) showed approximately double the frequency of genomic alterations compared with the lowest CSI quartile for ALK (16.2% vs. 8.7%), RET (12.8% vs. 6.9%), and MTOR (15% vs. 6.9%). Mid-range CSI values exhibited the lowest prevalence of alterations in EGFR (12.6% vs. 31%) and PIK3CA (6.9% vs. 14.5%). Overall, these findings support the value of CSI in refining exposure-genotype associations and the need for improves risk stratification efforts in diverse populations.</jats:p> </jats:sec> <jats:sec> <jats:title>Citation Format:</jats:title> <jats:p>Javiera Garrido, Evelin González, Alejandro Blanco, Gonzalo Sepúlveda-Hermosilla, Matias Freire, Solange Rivas, Katherine Marcelain, Gareth I. Owen, Carolina Ibañez, Alejandro H. Corvalan, Marcelo Garrido, Rodrigo Assar, Rodrigo Lizana, Javier Cáceres-Molina, Diego Ampuero, Liliana Ramos, Paola Pérez, Osvaldo Aren, Sara Chernilo, Cristina Fernández, María Loreto Spencer, Jacqueline Flores, Giuliano Bernal, Mónica Ahumada Olea, Germán Rasse, Carolina Sánchez, Maria Galli de Amorim, Emmanuel Dias-Neto, Helano C. Freitas, Ricardo Armisen. Effects of cumulative tobacco exposure on lung cancer genomic profiles in Latin Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6440.</jats:p> </jats:sec>
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