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Showing 6 results for Oncogene
Screening of prognostic factors using multiplex RT-PCR technique on different leukemic cell lines
Ahani R, Derakhshandeh Peykar P, Raoofian R, Heidari M,
Volume 67, Issue 1 (4-2009)
Abstract

Background: Leukemia is one of the most common pediatric malignancies. T-cell Acute Lymphoblastic Leukemia (T-ALL) accounts for 15% of hematopoetic cancers. It has been well understood that identification of genetic alterations associated with leukemias is very critical. The molecular genetic techniques have promoted the identification of leukemia-associated genetic changes that may characterize the most accurate predictors of clinical outcome. These considerations reinforce the requirement for rapid identification of the abnormalities.

Methods: Multiplex RT-PCR, a highly sensitive and specific method applied to screen simultaneously three most frequent transcription factors, TLX1/HOX11, TLX3/HOX11L2 and TAL1/SCL which are associated with T-cell Acute Lymphoblastic Leukemia (T-ALL).

Results: We describe here our efforts to establish a multiplex RT-PCR analysis system that facilitates the detection of HPB-ALL and K562 cell lines, respectively.

Conclusion: The multiplex RT-PCR technique is a sensitive, valuable and cost-effective diagnostic tool which could improve our ability to accurately and rapidly risk-stratification of patients with childhood T-ALL. In order to perform multiplex RT-PCR technique researchers do not need bone marrow samples and they can employ this method using peripheral blood samples. Therefore, the status of treatment could be followed by assessment of the level of mRNA expression of oncogenic transcriptional factor using peripheral blood sample. Use of this procedure not only provides the best results in short term for specialist, but also clinicians could have opportunities to choose suitable treatment strategies with decrement of drug side effects.


The frequency of G691S/S904S Haplotype of RET proto-oncogene in medullary thyroid carcinoma patients in Iranian population
Sara Sheikholeslami , Marjan Zarif Yeganeh, Laleh Hoghooghi Rad, Maryam Sadat Daneshpour, Mehdi Hedayati ,
Volume 72, Issue 8 (11-2014)
Abstract
Background: Medullary thyroid carcinoma (MTC) occurs in both sporadic (75%) and hereditary (25%) forms. The missense mutations of the rearranged during transfection (RET) proto-oncogene in MTC development have been well demonstrated. Several studies have been published that indicate the molecular analysis of RET gene may offer early identification of those patients at high risk to develop MTC and may provide the opportunity for early intervention. The aim of this study was to investigate frequency of G691S/S904S haplotype in MTC patients and their relatives. Methods: From 2004 to 2014, 358 participants were studied, including 213 patients (119 female, 94 male) and 145 their relatives (79 female, 66 male) in cellular and molecular research center of Shahid Beheshti Research Institute for Endocrine Sciences, Tehran, Iran. Genomic DNA was extracted from peripheral blood leucocytes using the standard Salting Out/Proteinase K method. Nucleotide change detection was performed using PCR and direct DNA sequencing methods. The RET mutations and SNPs, sequences were analyzed. Results: According to DNA sequencing results, 189 individuals (119 patients, 70 relatives) had both G691S (rs1799939) missense mutation in exon11 and S904S (rs1800863) synonymous mutation in exon 15 of RET proto-oncogene. The allele frequency of G691S/S904S haplotype was 35.02% in patients and 29.92% in their relatives. Conclusion: The obtained data showed the frequency of G691S/S904S RET gene haplotype among Iranian MTC patients and their relatives. The G691S and S904S nucleotide changes were in complete linkage disequilibrium, so the results were grouped together and referred to as G691S/S904S haplotype. This haplotype are not considered as oncogenic mutations at this time, its functional role should be investigated. Further analysis is needed to demonstrate the association between this haplotype and MTC development.
Germline mutation of exon 19 of RET proto-oncogene in an Iranian population with Medullary thyroid cancer
Hoda Golab Ghadaksaz , Mahmood Dehghani Ashkezari , Mehdi Hedayati ,
Volume 73, Issue 6 (9-2015)
Abstract
Background: Medullary thyroid cancer (MTC), includes 5-10% of all the thyroid cancers. RET proto-oncogene mutations have been found in association with MTC development. Therefore, identification of the mutations in RET can allow early diagnosis of the families who are at the risk of the disease. The goal of this study was to investigate existence and association between mutations in exon 19 of the RET proto-oncogene in an Iranian population medullary thyroid cancer patients and their family members. Methods: This study was run in the research laboratory of Research Institute for Endocrine Research Center Shahid Beheshti University of Medical Sciences from May, 2013 to May, 2014. In this study, 110 patients with confirmed medullary thyroid carcinoma were selected and examined. At first, the genomic DNA content of the peripheral white blood cells (WBC) of the samples were extracted using a saturated salting out and proteinase K standard method. Exon 19 of the RET proto-oncogene using polymerase chain reaction (PCR) method was amplified. Then the desired PCR products formation was confirmed by electrophoresis technique for true amplification, and finally the amplified samples were used for direct sequenced for finding and assessing any possible mutations Results: In this study, two nucleotide changes at position rs2075912 (Y: T/C) and position rs2075913 (W: T/A) exon 19 RET proto-oncogene were found in the patients with medullary thyroid cancer. The frequency of both nucleotide changes were higher in men than women with medullary thyroid cancer. The frequency of the rs2075912 and rs2075913 were 11.2 and 6.3% higher in men than women. But in statistical analysis, there was no association between age, sex and the founded two mutations. Conclusion: In addition to mutations in other exons of proto-RET, mutations in exon 19 can also be used for early detection and confirmation of medullary thyroid carcinomas.
Germline mutation of RET proto-oncogene’s exons 17 and 18 in Iranian medullary thyroid carcinoma patients
Marjan Zarif Yeganeh , Samira Kabiri , Sara Sheikholeslami , Hosna Hesanmanesh , Mehdi Hedayati ,
Volume 74, Issue 12 (3-2017)
Abstract

Background: Thyroid carcinoma is the most common endocrine malignancy. Medullary thyroid carcinoma (MTC) approximately accounts for 5-10% of all thyroid carcinoma. Nowadays, it is obviously, the mutations in REarranged during transfection (RET) proto-oncogene, especially, mutations in exons 10, 11 and 16 are associated with MTC pathogenesis and occurrence. Thus, early diagnosis of MTC by mutation detection in RET proto-oncogene allows to identify patients who do not have any developed symptoms. The aim of this study was to screening of germline mutations in RET proto-oncogene exons 17 and 18 in MTC patients and their first degree relatives in Iranian population.

Methods: In this cross-sectional study, three hundred eleven participates (190 patients, 121 their relatives) were referred to endocrine research center, Shahid Beheshti University of Medical Science during September 2013 until September 2015. The inclusion criteria were pathological and clinical diagnosis. After whole blood sampling, genomic DNA was extracted from peripheral blood leucocytes using the standard Salting Out/Proteinase K method. Nucleotide change detection in exons 17 and 18 was performed using PCR and direct DNA sequencing methods.

Results: In this study, twenty missense mutations [CGC>TGC, c.2944C>T, p.Arg982Cys (rs17158558)] which included 16 heterozygote and 4 homozygote mutations were found in codon 982 (exon 18). In the present study, 154 G>A (rs2742236) and 4 C>T (rs370072408) nucleotide changes were detected in exons 18 and intron 17 respectively. There was no mutation in exon 17.

Conclusion: It seems that because of arginine to cysteine substitutions in RET tyrosine kinase protein structure and its polyphen score (0.955) and SIFT score (0.01) the mutation in codon 982 (exon 18) could be have pathogenic effects. On the other hands, the mentioned mutation frequency was 6.4% among MTC patients, so this mutation of exon 18 could be checked in genetic screening tests of RET proto-oncogene. Although this needs more study.

Plasma levels of calcitonin in medullary thyroid carcinoma patients with and without the RET proto-oncogene mutations in exons 10 and 11
Samira Ehyayi , Mehdi Hedayati , Marjan Zarif Yeganeh , Sara Sheikholeslami , Sayed Asadollah Amini,
Volume 75, Issue 6 (9-2017)
Abstract
Background: Thyroid carcinoma is the most common endocrine malignancy and approximately accounts 2% of all cancer cases. Medullary thyroid cancer (MTC) is an endocrine tumor with differentiation of Parafollicular or C-cells and is categorized into hereditary or sporadic types. Medullary thyroid carcinoma approximately accounts for 5-10% of all thyroid carcinoma. Germ-line and somatic mutations in exons 10 and 11 RET (Rearranged during Transfection) proto-oncogene are responsible for the occurrence of the familial and sporadic types, respectively. Calcitonin is a key marker in MTC diagnose and has been demonstrated to be highly sensitive for differential diagnosis prognostic assessment, follow-up and evaluation of MTC treatment. The aim of this study was to investigate the relationship between plasma levels of calcitonin in MTC patients with or without RET mutation.
Methods: In this cross-sectional study, the population consist of MTC patients who have referred to the endocrine and metabolism research center of Shahid Beheshti University of medical sciences since October 2013 till October 2016. Genomic DNA was extracted from peripheral blood leucocytes using the standard salting out/proteinase K method. Nucleotide change detection in exons 10 and 11 was performed using polymerase chain reaction (PCR) and direct DNA sequencing methods. Participants were then divided into two groups with or without mutation (43 individuals in each group). Plasma calcitonin levels were determined by enzyme-linked immunosorbent assay (ELISA) method in both groups.
Results: Evaluation of the level of plasma calcitonin in 43 patients with a molecular mutation in RET proto-oncogene (mean age 31 years) and 43 patients without molecular mutations in RET proto-oncogene (mean age 43 years) were 7.6 pmol/mL and 3.07 pmol/mL respectively. This difference is statistically significant (P=0.0014).
Conclusion: Routine measurement of calcitonin has been investigated as a screening method for the diagnosis of medullary thyroid carcinoma patients. Nevertheless, additional data are required to definitely support routine measurement of calcitonin due to the role of RET proto-oncogene.

RET proto-oncogene mutations in the diagnosis of medullary thyroid cancer: a review article
Samaneh Hosseinzadeh, Safura Pakizehkar,
Volume 79, Issue 11 (2-2022)
Abstract
Medullary thyroid cancer accounts for 5-10% of thyroid carcinomas. RET proto-oncogene mutations occur in all of the hereditary MTCs and about 66% of the sporadic MTCs. So, the detection of the RET mutations is necessary for rapid and proper diagnosis and treatment. This systematic review seeks to find a comprehensive list of RET gene mutations in the diagnosis of medullary thyroid cancer.
The previous studies on RET proto-oncogene mutations in the diagnosis of medullary thyroid cancer were searched in the major databases including PubMed, Scopus, Medline, Embase and NCBI between 2010 and 2021.
Missense mutations in exons 10, 11, 13, 14, 15, and 16 of the RET proto-oncogene have the highest frequency in MTCs. The most common mutations in FMTC, are in codons 609, 611, 618, and 620 in exon 10, codon 768 in exon 13, codon 804 in exon 14, and codon 634 in exon 11. In the case of MEN2A, RET gene mutations have been observed in exons 5, 8, 10, 11, with the highest mutations in exons 10 (codons 609, 611, 618, and 620) and exon 11 (codons 630 and 634). Moreover, M918T mutation in exon 16 and A883F mutation in exon 15 have been detected in 95% and 5% of the patients with MEN2B respectively. In the case of MTC, the M918T mutation in exon 16 is the most common mutation, which is associated with a poor prognosis. RET genetic screening is crucial for an exact approach to the diagnosis and treatment of MTC. Anyone with MTC, even without a family history of MEN2, should be genetically tested for the RET mutations to confirm or rule out the inherited disease and, if necessary, preventive thyroidectomy. This systematic review provided a comprehensive list of the reported mutations in the RET gene for the diagnosis of medullary thyroid cancer.
 

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