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PURPOSE: Multidisciplinary molecular tumor boards (MTBs) decode complex genomic data into clinical recommendations. Although MTBs are well-established in the oncology practice in developed countries, this strategy needs to be better explored in developing countries. Herein, we describe the possible benefits and limitations of the first MTB established in Colombia. METHODS: Demographic, clinical, and genomic information was collected between August 2020 and November 2021. By mid-2020, an MTB strategy was created to discuss clinical cases with one or more genomic alterations identified by next-generation sequencing using an open-access virtual platform. We characterized the patient population as benefiting from the recommended treatment option. We assessed the benefits and access to available targeted therapies that have the potential to change clinical management by making recommendations to treating oncologists on the basis of genomic profiling. However, we did not assess the treatment oncologists' compliance with MTB recommendations because they were not intended to replace clinical judgment/standard of care. RESULTS: A total of 146 patients were included in the discussions of the MTB. The median age was 59 years, and 59.6% were women. Genomic results prompting a change in therapeutic decisions were obtained in 53.1% of patients (95% CI, 44.9 to 61.3). The most prevalent malignancy was non-small-cell lung cancer (51%). Other malignancies represented 60%, 50%, and 30% of patients with soft-tissue sarcomas, brain tumors, and breast cancer, respectively. CONCLUSION: Using an open-access virtual platform, MTBs were feasible in low- and middle-income countries on the basis of the capability to provide the benefits and access to available targeted therapies that are not standard of care. Furthermore, MTB recommendations were made available to the treating oncologist in different locations across Colombia, providing the option to modify clinical management in most of these patients.
Assuntos
Hispânico ou Latino , Neoplasias , Avaliação de Resultados em Cuidados de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Mama , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Oncologia , Sarcoma , Neoplasias Encefálicas , Neoplasias de Tecidos Moles , Neoplasias/terapia , Resultado do TratamentoRESUMO
Introducción: la apolipoproteína E (APOE) es una glicoproteína implicada en el transporte de moléculas lipídicas. Se han descrito tres alelos del gen APOE: Æ2, Æ3 y Æ4. Varios estudios demuestran asociación de la isoforma APOE4 con Alzheimer de inicio tardío. Objetivos: determinar las frecuencias genotípicas y alélicas del gen APOE en una muestra de adultos en Bogotá. Materiales y métodos: estudio observacional descriptivo de corte transversal. A partir de una muestra de sangre periférica se extrajo ADN genómico y se realizó PCR-Tetraprimer para la determinación de los alelos de APOE. Resultados: se incluyeron 1.254 sujetos, 942 mujeres (75%) y 312 hombres (25%) con edades entre 40 y 100 años. El alelo más frecuente fue el Æ3 (85%), seguido por Æ4 (11%) y Æ2 (2%). De la población que manifestó tener ascendencia cundiboyacense, 567 sujetos (74.6%) presentaban el genotipo Æ3/Æ3, mientras que 156 (20.4%) el Æ3/Æ4, 23 (3%) el Æ2/Æ3, 11 (1.5%) el Æ4/Æ4y 4 (0.5%) el Æ2/Æ4. Los individuos con genotipoÆ2/Æ2 manifestaron no conocer el dato de ascendencia. Conclusiones: las frecuencias alélicas y genotípicas de APOE varían según el origen étnico, sin embargo es posible la identificación de sujetos con el genotipo menos frecuente (Æ2/Æ2) al analizar muestras de mayor tamaño. En los reportes previos en el país no se ha descrito el genotipo Æ2/Æ2, el cual fue identificado en la presente muestra como el de menor proporción.
Introduction:apolipoprotein E (APOE) is a glycoprotein involved in the transport of lipid molecules. Three alleles of the APOE gene have been described: Æ2, Æ3 and Æ4. Several studies show an association of the APOE isoform with late-onset Alzheimer Ìs disease. Objectives: to determine the genotypic and allelic frequencies of the APOE gene in an adult sample in Bogotá. Materials and Methods: a cross-sectionalobservational descriptive study. Genomic DNA was extracted from a peripheral blood sample and APOE alleles and genotypes were determined using the PCR tetra-primer method. Results:we included 1254 subjects, 942 women (75%) and 312 men (25%) aged between 40 and 100 years. The most frequent allele was Æ3 (85%), followed by Æ4 (11%) and Æ2 (2%). Of the population that declared to have Cundinamarca and Boyacá sub-regions ancestry, 567 subjects (74.6%) had genotype Æ3/Æ3, while 156 (20.4%) hadÆ3/Æ4, 23 (3%) Æ2/Æ3, 11 (1.5%) Æ4/Æ4and 4 (0.5%) had genotype Æ2/Æ4.The individuals with genotype Æ2/Æ2 declared not to know the data on their ancestry. Conclusions: the allelic and genotypic frequencies of APOE vary according to ethnic origin. However identifying subjects with the less frequent genotype (Æ2/Æ2) is possible when analyzing larger samples. In previous reports in the country, genotype Æ2/Æ2, has not been described and was identified in the present sample as the one with the lowest proportion.
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Apolipoproteínas E , Reação em Cadeia da Polimerase , Doença de Alzheimer , Isoformas de ProteínasRESUMO
We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica). In total, 87% (26/30) of the participating centres/registries belonging to the nine countries are performing genetic testing. Overall, 1352 suspected families were sequenced. Pathogenic variants were identified in 34% of the families, with slightly differing distribution of variants between females and males. Path_MLH1 variants were identified in 39% of females and 50% of males (p = 0.023), while path_MSH2 were identified in 37% of females and males, followed by path_PMS2 in 11% of females and 8% of males, path_MSH6 in 13% of females and 3% of males (p < 0.001) and path_EPCAM in 0.3% of females and 2% of males. In Latin America, 9 of 12 (75%) participating countries had implemented healthcare for LS. LS screening is inconsistently applied within Latin America healthcare systems because of structural differences in the healthcare systems between the countries.
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Neoplasias Colorretais Hereditárias sem Polipose/genética , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Sistema de Registros/estatística & dados numéricos , Inquéritos e Questionários , Adulto , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Proteínas de Ligação a DNA/genética , Molécula de Adesão da Célula Epitelial/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , América do Sul , Adulto JovemRESUMO
Here we report a case of a young, never-smoker Hispanic woman with a hereditary familial overlap syndrome (Li-Fraumeni plus CDH1). The patient developed multiple synchronous primary lung adenocarcinomas related to Intra-Alveolar Tumor Spread (STAS) several years after the diagnosis of a locally advanced lower limb osteosarcoma. Comprehensive genomic profiling by next generation sequencing (NGS) was performed on 90 cancer-related genes over each lung lesion (including two nodules of acinar adenocarcinoma, one lepidic spread tumor and in the STAS area). Likewise, the broad genomic analysis was performed on archival tissue from the previous bone tumor. Lung tumors were found to harbor PIK3CA (invasive lesions) and a rare in-frame insertion of nucleotides in exon 19 of EGFR (lepidic tumor). STAS area showed KRAS and BRAF mutations in two different segments, and osteosarcoma tested positive for well known PIK3CA, KRAS and CDH1 alterations. This unique case raises practical questions as to the challenges of molecular testing and highlights the potential association of germline TP53 and CDH1 mutations with concurrent somatic alterations that elucidate the basis of tumor heterogeneity.
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Adenocarcinoma/diagnóstico , Síndrome de Li-Fraumeni/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Adulto , Antígenos CD/genética , Caderinas/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Receptores ErbB/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Síndrome de Li-Fraumeni/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto JovemRESUMO
Multiple hereditary exostoses (MHE) is a rare disease with autosomal dominant inheritance, caused by heterozygous germline mutations in the EXT1 or EXT2 genes. This disorder is characterized by the growth of prominences surrounded by cartilage in the growth plates and the long bones. Here, we report a family affected by MHE. In this family, a pathogenic variant c.544C > T (p. Arg182Ter) was identified in the EXT2 gene. This variant has been previously described in the literature, and here we are reporting the relationship with clinical findings. MHE is suspected according to the clinical manifestations; molecular research should be performed to establish the most frequent mutations. A support, diagnosis, and follow-up group should be created, and genetic counseling should be available for patients and families.
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[This corrects the article DOI: 10.1055/s-0038-1636998.].