ABSTRACT
Early-onset Alzheimer's disease (EOAD), defined as Alzheimer's disease onset before 65 years of age, has been significantly less studied than the "classic" late-onset form (LOAD), although EOAD often presents with a more aggressive disease course, caused by variants in the APP, PSEN1, and PSEN2 genes. EOAD has significant differences from LOAD, including encompassing diverse phenotypic manifestations, increased genetic predisposition, and variations in neuropathological burden and distribution. Phenotypically, EOAD can be manifested with non-amnestic variants, sparing the hippocampi with increased tau burden. The aim of this article is to review the different genetic bases, risk factors, pathological mechanisms, and diagnostic approaches between EOAD and LOAD and to suggest steps to further our understanding. The comprehension of the monogenic form of the disease can provide valuable insights that may serve as a roadmap for understanding the common form of the disease.
ABSTRACT
We searched for the prevalence of actionable somatic mutations in exon 2 of the KRAS gene in western Mexican patients with CRC. Tumor tissue DNA samples from 150 patients with sporadic CRC recruited at the Civil Hospital of Guadalajara were analyzed. Mutations in exon 2 of the KRAS gene were identified using Sanger sequencing, and the data were analyzed considering clinical-pathological characteristics. Variants in codon 12 (rs121913529 G>A, G>C, and G>T) and codon 13 (rs112445441 G>A) were detected in 26 patients (with a prevalence of 17%). No significant associations were found between these variants and clinical-pathological characteristics (p > 0.05). Furthermore, a comprehensive search was carried out in PubMed/NCBI and Google for the prevalence of KRAS exon 2 mutations in Latin American populations. The 17 studies included 12,604 CRC patients, with an overall prevalence of 30% (95% CI = 0.26-0.35), although the prevalence ranged from 13 to 43% across the different data sources. Determining the variation and frequency of KRAS alleles in CRC patients will enhance their potential to receive targeted treatments and contribute to the understanding of the genomic profile of CRC.
ABSTRACT
Resumen Los piRNA son secuencias de 24 a 32 nucleótidos asociados a proteínas PIWI de la familia argonauta, la cual posee propiedad endonucleasa. Son sintetizados a partir de regiones intergénicas repetitivas y su principal función, es el silenciamiento de transposones, sin embargo, se ha encontrado que su descontrol está asociado con el desarrollo de diversos tipos de cáncer. Varios piRNAs han sido propuestos como biomarcadores del desarrollo tumoral, sin embargo, no en todos los tipos de cáncer han sido estudiados, siendo el cáncer de mama y el cáncer gástrico los que encabezan la lista con un mayor número de publicaciones. El presente trabajo, se centra en conocer los piRNAs de mayor relevancia en tipos específicos de cáncer con la finalidad de promover su análisis en casos de cáncer en los que han sido poco estudiados, o que predominan epidemiológicamente en ciertas poblaciones.
Abstract The piRNAs are sequences from 24 to 32 nucleotides associated with PIWI proteins from the Argonauta family, which possesses endonuclease holdings. They are synthesized from repetitive intergenic regions and their main function is the silencing of transposons, however, it has been found that its lack of control is associated with the development of various types of cancer. Several piRNAs have been associated as biomarkers of tumor development, however, It has not been studied in all types of cancer, recent investigations show that breast and gastric cancer are on top of the list with more publications related with piRNAs. Therefore, the present review focuses on knowing the most relevant piRNAs in specific types of cancer, in order to promote their analysis in the poorly studied cancer or that predominate epidemiologically in certain populations.