Browsing by Author "Corvalán Rodríguez, Alejandro"

Now showing 1 - 8 of 8
  • Thumbnail Image
    Item
    Beyond tobacco: genomic disparities in lung cancer between smokers and never-smokers
    (Springer Nature, 2024) Garrido, Javiera; Bernal, Yanara; González, Evelin; Blanco, Alejandro; Sepúlveda-Hermosilla, Gonzalo; Freire, Matías; Oróstica, Karen; Rivas, Solange; Marcelain, Katherine; Owen, Gareth Ivor; Ibáñez Cáceres, Carolina; Corvalán Rodríguez, Alejandro; Garrido, Marcelo; Assar, Rodrigo; Lizana, Rodrigo; Cáceres-Molina, Javier; Ampuero, Diego; Ramos, Liliana; Pérez, Paola; Aren, Osvaldo; Chernilo, Sara; Fernández, Cristina; Spencer, María L.; Aguila, Jacqueline F.; Dossetto, Giuliano B.; Olea, Mónica A.; Rasse, Germán; Sánchez, Carolina; Amorim, Maria Galli de; Bartelli, Thais F.; Nunes, Diana N.; Dias-Neto, Emmanuel; Freitas, Helano C.; Armisén, Ricardo
    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.
  • No Thumbnail Available
    Item
    Factores de riesgo de alteraciones citológicas del cuello uterino en mujeres Chilenas: Un estudio de casos y controles
    (2010) Solís, M. T.; Aguayo González, Francisco Renan; Vargas, M.; Olcay, F.; Puschel Illanes, Klaus; Corvalán Rodríguez, Alejandro; Ferreccio Readi, Catterina
  • Thumbnail Image
    Item
    Genotipos de virus papiloma humano (VPH) en pacientes con cáncer cérvico-uterino en un hospital público y una clínica privada de Santiago, Chile
    (2010) Valdivia Leiva, Isabel Margarita; Aguayo González, Francisco Renan; Pruyas A., Martha; Snijders, Peter J. F.; Corvalán Rodríguez, Alejandro; Ferreccio Readi, Fresia Catterina
    We compared HPV genotypes among squamous cervical cancer samples from a public hospital (n = 55) and a private clinic (n = 35 cases) of Santiago. Paraffin-embedded specimens were analyzed by PCR followed by an immunoenzimatic assay. Reverse line blotting was used for the identification of 36 HPV genotypes. We found HPV DNA in 94.4% of all cancers. Single infections: HPV16: 40.0%, (clinic 37.1%, hospital 41.8%) VPH18:7.8% (clinic 2.9%, hospital 10.9%); single+multiple infections: VPH16: 61.1% (clinic 53.1%, hospital 71.7%), VPH18: 34.4% (clinic 21.9%, hospital 45.2%). HPV16 or HPV18 occurred in 75.6% of cases, higher in the hospital than the clinic (87.3%-95% CI: 84.9-96.3 - and 57.1%-95% CI: 46.6-66 - respectively, p = 0.002). Other genotypes in single infections: HPV 26, 31, 33, 45, 58, 67; in co-infections: HPV 35,52,56,59 and 66. HPV16 but specially HPV18 were significantly more frequent in the public hospital; 75.6% of squamous cervical cancer were associated to the vaccine preventable HPV16/18.
  • No Thumbnail Available
    Item
    Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis
    (Baishideng Publishing Group Inc., 2015) Valenzuela, Manuel A.; Canales, Jimena; Corvalán Rodríguez, Alejandro; Quest, Andrew F. G.
    The sequence of events associated with the development of gastric cancer has been described as "the gastric precancerous cascade". This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia. According to this model, Helicobacter pylori (H. pylori) infection targets the normal gastric mucosa causing non-atrophic gastritis, an initiating lesion that can be cured by clearing H. pylori with antibiotics or that may then linger in the case of chronic infection and progress to atrophic gastritis. The presence of virulence factors in the infecting H. pylori drives the carcinogenesis process. Independent epidemiological and animal studies have confirmed the sequential progression of these precancerous lesions. Particularly long-term follow-up studies estimated a risk of 0.1% for atrophic gastritis/intestinal metaplasia and 6% in case of dysplasia for the long-term development of gastric cancer. With this in mind, a better understanding of the genetic and epigenetic changes associated with progression of the cascade is critical in determining the risk of gastric cancer associated with H. pylori infection. In this review, we will summarize some of the most relevant mechanisms and focus predominantly but not exclusively on the discussion of gene promoter methylation and miRNAs in this context.
  • No Thumbnail Available
    Item
  • No Thumbnail Available
    Item
    Mismatch repair expression in testicular cancer predicts recurrence and survival
    (2008) Velasco Palma, Alfredo Alejandro; Corvalán Rodríguez, Alejandro; Wistuba, Ignacio I.; Riquelme, Erick; Chuaqui, Rodrigo; Majerson Grinberg, Alejandro; Leach, Fredrick S.
    We investigated mismatch repair (MMR) gene expression in testicular cancer as a molecular marker for clinical outcome (recurrence, response to chemotherapy and death) using protein expression and specific genetic alterations associated with the presence or absence of MMR activity. One hundred sixty-two cases of paraffin-embedded testis cancer specimens were subjected to immunohistochemical analysis using monoclonal antibody for MLH1 and MSH2 MMR proteins and genetic analysis using specific polymorphic markers. The degree of MMR immunoreactivity and genetic instability in the form of loss of heterozygosity (LOH) and/or microsatellite instability (MSI) were determined by comparing matched normal and tumor tissue. The degree of immunohistochemical staining for MMR expression was associated with a shorter time to tumor recurrence, resistance to chemotherapy and death. Furthermore, clinical relapse and cancer specific death was also associated with tumors exhibiting a high degree of MSI, p = 0.01 and 0.04, respectively. In contrast, LOH was not associated with recurrence, resistance to chemotherapy or death. Therefore, MMR expression defines testis cancers with distinct molecular properties and clinical behavior, such that tumors with decreased MMR immunostaining and/or increased frequency of MSI have a shorter time to recurrence and death despite chemotherapy. (c) 2007 Wiley-Liss, Inc.
  • Thumbnail Image
    Item
    Teneurin protein family: an emerging role in human tumorigenesis and drug resistance
    (2012) Ziegler, Annemarie; Corvalán Rodríguez, Alejandro; Roa, Iván; Brañes Yunusic, Jorge Antonio; Wollscheid, Bernd
    Using a chemoproteomic strategy, we recently demonstrated the expression of teneurin-2, a transmembrane glycoprotein, in the majority of malignant mesothelioma cell lines. This finding was unexpected since no formally organized evidence existed to implicate teneurins in human malignancy. For this reason, here we provide a comprehensive review on the expression of teneurins in human tumors and cell lines. Current evidence supports the aberrant expression of teneurins in various tumor types, their involvement in cancer-related regulatory networks, and their potential participation in drug resistance. Structural attributes of teneurins could enable the detection of shedded forms in body fluids for clinical applications. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
  • Thumbnail Image
    Item
    The Phylogeographic Diversity of EBV and Admixed Ancestry in the Americas-Another Model of Disrupted Human-Pathogen Co-Evolution
    (2019) Corvalán Rodríguez, Alejandro; Ruedlinger, Jenny; Mayo, Tomás de; Polakovicova, Iva; González-Hormázabal, Patricio; Aguayo, Francisco
    Epstein-Barr virus (EBV) is an etiological agent for gastric cancer with significant worldwide variations. Molecular characterizations of EBV have shown phylogeographical variations among healthy populations and in EBV-associated diseases, articularly the cosegregated BamHI-I fragment and XhoI restriction site of exon 1 of the LMP-1 gene. In the Americas, both cosegregated variants are present in EBV carriers, which aligns with the history of Asian and European human migration to this continent. Furthermore, novel recombinant variants have been found, reflecting the genetic makeup of this continent. However, in the case of EBV-associated gastric cancer (EBV-associated GC), the cosegregated European BamHI-“i” fragment and XhoI restriction site strain prevails. Thus, we propose that a disrupted coevolution between viral phylogeographical strains and mixed human ancestry in the Americas might explain the high prevalence of this particular gastric cancer subtype. This cosegregated region contains two relevant transcripts for EBV-associated GC, the BARF-1 and miR-BARTs. Thus, genome-wide association studies (GWAS) or targeted sequencing of both transcripts may be required to clarify their role as a potential source of this disrupted coevolution.