Recurrent Regional Allelic Imbalance in Chromosome 15 in Rat Endometrial Adenocarcinomas
YAKHTEH
Authors: Hamta, Ahmad; Talebbeigy, Farah
Abstract
Objective: Animals of the inbred BDII rat strain are genetically predisposed to endometrial adenocarcinomas (EAC) and can be used to model human cancer. From our previous studies, it was obvious that some chromosomes were selectively involved in EAC development; one of them was rat chromosome (RNO) 15, in which there were often losses in the short arm and gains in the long arm. Since cytogenetic events lead to allelic imbalance and/or loss of heterozygosity (Al/LoH) in RNO15, it was subjected to a detailed analysis with polymorphic microsatellite markers spanning the entire chromosome. Materials and Methods: BDII/Han females were crossed to males from two other inbred rat strains known to have low incidence of EAC (BN/Han and SPRD-Cu3/Han). DNA extracted from F1, F2 and backcross offspring were used in this studies. Our final marker panel consisted of 36 markers. Results: The analysis showed that Al/LoH was common in EAC tumors and was concentrated to four well-defined regions along the chromosome. Two of these regions were close to the distal end of the short arm; one region was in the middle of the chromosome, probably spanning the centromere; and the fourth region was located distally in the long arm. Conclusion: According to the Rat Genome Project (RGP), the number of genes in these regions approached 300. According to a database search, about 80 of these genes could be considered 'cancer-related" and they were potential candidates to be targets for the observed chromosomal aberrations. Among the cancer-related genes, there were Anxa7 (Region I), Bmp4, Lgals3, Cd-kn3 (Region II), Rb1, Ddx26, Clu, Bnip3, Nkx3.1 (Region III), and Gpc5 (Region IV).
Influence of LGALS3 and PNPLA3 genes in non-alcoholic steatohepatitis (NASH) in patients after bariaric surgery
OBESITY RESEARCH & CLINICAL PRACTICE
Authors: Foinquinos, Gabriela Azevedo; Azevedo Acioli, Maria Eduarda; Santana Cavalcanti, Antonio Henrique; Barbosa Junior, Walter Lins; Lima, Raul Emidio; Juca, Norma Thome; de Azevedo Foinquinos, Rosa Cirne; da Cruz, Clarissa Rocha; Fernandez Pereira, Fernanda Maria; de Carvalho, Sylene Rampche; de Mendonca Belmont, Taciana Furtado; Silva Vasconcelos, Luydson Richardson; Moreira Beltrao Pereira, Leila Maria
Abstract
Aim: This study evaluated the genesPNPLA3 and LGALS3 in patients who have undergone bariatric surgery. Methods: Individuals with NAFLD and NASH were evaluated, the DNA was extracted from total blood for genotyping of rs4644, rs4652 from LGALS3 and rs738409 from PNPLA3 genes, the total RNA was obtained from liver biopsy. For the detection of the molecular targets, real-time PCR through Taqman probes was used. Results: From a total of 46 collected patients, of those 21 (456%) were included as NASH and 25 (544%) as steatosis group. This groups showed significant difference to aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Glutamyl transpeptidase (GGT) (p = 0.0108, p = 0.0090 and p = 0.0044). Regarding to gene expression in studied groups, hepatic steatosis vs NASH, we observed a higher expression of the LGALS3 gene in NASH (p = 0.0273). In addition, patients with C allele in homozygous for rs4644 and rs4652 of LGALS3 gene had higher expression, in NASH group (p = 0.0500 and p = 0.0242, respectively), furthermore for rs4644 both alleles in homozygous showed higher expression (AA/CC vs AC) (p = 0.0500), when analyzed PNPLA3 rs738409, NASH patients with G allele in homozygous had higher expression (p = 0.0494). Conclusions: Therefore, an increased expression of the LGALS3 gene in patients with NASH may be important in the etiopathogenesis of the disease, as well as the presence of rs4652 and rs4644 SNPs in the regulation of transcriptional levels of the gene in patients with NAFLD and NASH. (C) 2020 Published by Elsevier Ltd on behalf of Asia Oceania Association for the Study of Obesity.