ABSTRACT
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.
Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Genetic Predisposition to Disease/genetics , Genetic Testing/methods , Registries/statistics & numerical data , Surveys and Questionnaires , Adult , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , DNA-Binding Proteins/genetics , Epithelial Cell Adhesion Molecule/genetics , Female , Humans , Male , Middle Aged , MutL Protein Homolog 1/genetics , MutS Homolog 2 Protein/genetics , South America , Young AdultABSTRACT
Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%-80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency.
Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , MutL Protein Homolog 1/genetics , MutS Homolog 2 Protein/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Early Detection of Cancer , Female , Guideline Adherence , Humans , Latin America/epidemiology , Male , Practice Guidelines as Topic , Risk AssessmentABSTRACT
la hibridación in situ por fluorescencia (FISH) se considera una técnica citogenética molecular, que revolucionó los análisis cromosómicos dentro de la citogenética humana, y surge como una técnica muy promisoria en el campo de la genética clínica, oncología, patología y en la investigación básica. En la actualidad tiene gran aceptación en el diagnóstico clínico debido a su alta especificidad, sensibilidad y rapidez en la identificación de alteraciones cromosómicas en diferentes tipos de tejidos.Una de las grandes ventajas que tiene el FISH sobre la citogenética convencional es la de poder realizar estudios cromosómicos en núcleos interfásicos, lo cual hace posible un resultado en 24 horas sin la necesidad de establecer cultivos celulares.La citogenética del cáncer es una disciplina donde el FISH tiene una gran aplicación, en cuanto a que resuelve cariotipos complejos que se tienen con las técnicas convencionales, especialmente en la identificación de translocaciones crípticas y marcadores Por otra parte, se pueden realizar análisis sobre la amplificación de protooncogenes y genes supresores de tumor en núcleos interfásicos o en secciones de tejidos tumorales en fresco o incluidos en parafina. Lo anterior representa una ventaja para un tamizaje rápido de muchas enfermedades, entre ellas el cáncercromosómicos recurrentes en determinadas neoplasias
