Investigation of Mutations of Exon 11-A of BRCA1 Gene in Women with Breast Cancer in the Northwest of Iran

BACKGROUND AND OBJECTIVE: Breast cancer is the most common cancer in women, which is associated with genetic changes such as mutations in carcinogenic genes and tumor suppressor genes. One of the most important tumor suppressor genes involved in breast cancer is the BRCA1 gene. The mutation in this gene is a common occurrence in human breast cancer. The purpose of this study is to investigate the mutations of exon 11-A of BRCA1 gene in women with breast cancer in the northwest of Iran. METHODS: In this descriptive study, blood sample were collected form 40 patients with breast cancer whose cancer was diagnosed before the age of 40 years and the exon 11-A of BRCA1 gene was examined using PCR and direct sequencing methods to detect mutations. Sequencing results were analyzed using Chromas software. FINDING: In the present study, a nonsynonymous mutation was reported as a new mutation of BRCA1 gene for the first time: Ala584Thr mutation was also observed in two samples. The mutations of codon 694 (Ser694Ser) showed a higher incidence (52.5%). Other mutations were observed in codons 693, 356, 486, 550 and 628. CONCLUSION: Based on the results of this study, mutations and polymorphisms of exon 11 of BRCA1 gene were observed for the first time in the northwestern population of Iran. One new case of mutation was observed in exon 11-A of BRCA1 gene

Comparison between the Plasma Levels of Long Noncoding RNA BDNF-AS in Patients with Alzheimerś disease and Healthy Subjects

BACKGROUND AND OBJECTIVE: Diagnosis of Alzheimer's disease usually occurs when serious damages have occurred in the brain and common treatments are ineffective in preventing it. One of the RNAs involved in Alzheimer's disease is a long noncoding RNA, called BDNF antisense (BDNF-AS). The aim of this study is to determine the presence and compare the BDNF-AS levels in plasma of Alzheimer's patients and healthy subjects, and to evaluate its potential as a plasma marker for Alzheimer's disease. METHODS: In this case-control study, 30 patients with late-stage Alzheimer's disease and 30 healthy subjects without neurological disease who matched the patients in terms of age were selected by a specialist according to the criteria for clinical diagnosis of Alzheimer's disease and their intravenous blood samples were collected. The plasma of the blood samples was isolated and total plasma RNA was extracted. After cDNA synthesis, the presence of BDNF-AS in plasma was examined by PCR. Finally, the relative level of BDNF-AS transcripts in plasma samples of patients with Alzheimer's disease and healthy subjects was evaluated using Real Time PCR. FINDINGS: The results of this study showed that long noncoding RNA BDNF-AS was present in the plasma of patients and controls. Comparison of Real Time PCR data showed that BDNF-AS levels in the plasma of patients (0.107±0.021) showed significant increase compared to healthy subjects (0.039 ± 0.006). CONCLUSION: The results of this preliminary study indicate that the levels of long noncoding RNA BDNF-AS in plasma can be used as a blood/plasma marker for the diagnosis of Alzheimer's disease

The Study of Long Noncoding RNA, Meg3, Expression Level and Its Association with Clinicopathologic Features in Breast Cancer

BACKGROUND AND OBJECTIVE: Breast cancer is the most common invasive cancer and the second main cause of cancer death in women. Long noncoding RNAs (lncRNAs) play a critical role in different cellular and molecular activities such as carcinogenesis. Maternally Expressed Gene 3 (MEG3), is a long noncoding RNA that deregulates in various types of cancers. The aim of this study is the evaluation of MEG3 expression level and its association with clinicopathological features of breast tumor tissues. METHODS: In this case-control study, 40 fresh-frozen breast tumor specimens and their paired non-tumoral adjacent tissues were collected from breast cancer patients living in the northwestern region of Iran. All tumor samples belonged to the invasive ductal carcinoma. After RNA extraction and cDNA synthesis, the expression level of MEG3 in breast tumor tissues compared to the paired adjacent normal tissues was investigated using specific primers and quantitative real-time PCR (qRT-PCR). β2m was also used as an internal control for normalization. FINDINGS: MEG3 expression level in all tumor samples significantly downregulated compared to the paired adjacent nontumoral specimens, with an average fold decrease of 3.355(p=0.042). Low level of MEG3 in tumor tissues was also related to the age of patients (p=0.007), stage III (p=0.049) and lymph node metastasis (p=0.018). CONCLUSION: The expression level of MEG3 significantly decreased in breast cancer and this downregulation was related to malignancy state of the tumor