Search

Background: This study was designed and performed to investigate the relationship between fetal chromosome aberrations and screening markers in the first trimester of pregnancy in order to prevent the birth of infants with chromosome aberrations with early prenatal diagnosis. Methods: We conducted an analytic cross-sectional study on result of chromosomal culture of 762 pregnant women with high-risk combined screening test from December 2018 to June 2020 and analyzed by SPSS program. Results: There was a significant relationship between chromosome structural abnormalities with free beta-human chorionic gonadotropin (free β-hCG) values equal to and higher than 1.5 multiples of the median (MoM) (P: 0.05). The highest incidence of disorder in number of chromosomes with abnormal nuchal translucency (NT) percentiles (≥99%) was seen (P < 0.001). It also shows that the cumulative number of chromosome aberrations of 25 (78.12%) occurred in individuals with a NT less than 99th percentile and at the same time a risk of 1/50≤ risk <1/10. Discussion: According to the results, Comparative Genomic Hybridization (CGH) array method is recommended to detect structural abnormalities in chromosomes in samples with NT ≥3.5. In addition, it is noteworthy that chromosomal structural abnormalities occur in free β-hCG ≥1.5 MoM. Conclusion: Due to the frequency of chromosomal structural disorders and its effect on the incidence of fetal abnormalities, the study of chromosomal structural disorders is recommended. [ABSTRACT FROM AUTHOR]

Background: The promoter methylation and single nucleotide polymorphisms (SNPs) affect the transcription activity of cancer-related genes in several cancers including diffuse gastric cancer (DGC). Here we aimed to evaluate the promoter methylation status and the rs16260 at the promoter region of the CDH1 gene in DGC. Methods: This case-control study was performed of 48 formalin-fixed paraffin-embedded (FFPE) blocks of DGC patients and 41 fresh frozen tissue samples of healthy individuals. Methylation status was evaluated using methylation-specific polymerase chain reaction (PCR) and the rs16260 at the promoter region of the CDH1 gene was assessed using PCR and sequencing method. Results: The occurrence of methylation at the promoter region of the CDH1 gene in DGC patients was significantly higher than control samples (P < 0.0001). The methylated status was significantly associated with the poor differentiated histological type of DGC (P = 0.0428). The frequency of AC genotype and the A allele in DGC patients was significantly higher than the control subjects (P = 0.006 and 0.003, respectively). Conclusions: Here we showed that methylation at the CDH1 promoter may contribute to the DGC development, and also the AC genotype was associated with the risk of DGC. [ABSTRACT FROM AUTHOR]

Aim: we aimed to evaluate somatic mutations of CTNNA1 in DGC patients. Background: Diffuse gastric cancer (DGC) is a major type of gastric cancer where most cases are sporadic diffuse gastric cancer (SDGC). It has been shown that mutations in CTNNA1 are responsible for some cases of hereditary diffuse gastric cancer (HDGC). Methods: In the present work, 48 formalin-fixed paraffin-embedded tissues, including samples of 38 SDGC and 10 HDGC patients were examined through Sanger sequencing approach on PCR products amplified from 18 exons and boundaries of intron/exon of CTNNA1 gene. Results: We revealed 9 novel somatic mutations in CTNNA1 gene in patients with HDGC and SDGC, from which one variant was intronic. Eight patients had at least one disease-causing mutation (16.6%). Most of the patients were in the III stage of cancer (50%). Except for one patient, histological type of the rest of mutation-harboring patients was signet ring cell carcinoma, and only one HDGC patient had CTNNA1 mutation. Conclusion: Our study showed several novel variants in the CTNNA1 gene in Iranian sporadic and hereditary DGC patients, and implies that the CTNNA1 gene mutations could be involved in the pathogenesis of DGC, either hereditary or in sporadic cases. [ABSTRACT FROM AUTHOR]

Background: Hereditary diffuse gastric cancer (HDGC) is a hereditable form of diffuse gastric cancer with very aggressive tumors, poor prognosis, and delayed clinical signs. Method: We assessed 17 probands identified with HDGC upon gastrectomy according to the histopathological criteria confirmed by a pathologist and familial history. We extracted DNA from peripheral blood and formalin fixed paraffin-embedded tissues. DNA sequencing was done following PCR amplification of 16 exons and exon/intron boundaries of the CDH1 gene and exon 2 of CTNNA1 gene. The Multiplex Ligation-dependent Probe Amplification technique was performed on patients with no pathogenic variants in sequencing. Results: Totally, 17 probands comprising seven males and 10 females were assessed. In three patients, we recognized the tumors in the early TNM stage (I, II), while in 14 cases, tumors were observed in the late stages (III, IV). Overall, DNA sequencing of the CDH1 gene identified 16 variants (seven exonic including five new variants and nine intronic containing six new variants). Moreover, Multiplex Ligation-dependent Probe Amplification detected one deletion in exon 1 of two patients. Conclusion: Our results showed that E-cadherin deficiency in HDGC was related to CDH1 gene point mutations and large deletion with high heterogeneity, which should be considered in the diagnosis and treatment of HDGC patients. [ABSTRACT FROM AUTHOR]