Tumor circulating biomarkers in colorectal cancer.

CRC is a major global health concern and is responsible for a significant number of cancer-related deaths each year. The successful treatment of CRC becomes more difficult when it goes undetected until it has advanced to a later stage. Diagnostic biomarkers can play a critical role in the early detection of CRC, which leads to improved patient outcomes and increased survival rates. It is important to develop reliable biomarkers for the early detection of CRC to enable timely diagnosis and treatment. To date, CRC detection methods such as endoscopy, blood, and stool tests are imperfect and often only identify cases in the later stages of the disease. To overcome these limitations, researchers are turning to molecular biomarkers as a promising avenue for improving CRC detection. Diagnostic information can be provided more reliably through a noninvasive approach using biomarkers such as mRNA, circulating cell-free DNA, micro-RNA, long non-coding RNA, and proteins. These biomarkers can be found in blood, tissue, feces, and volatile organic compounds. The identification of molecular biomarkers with high sensitivity and specificity for early detection of CRC that are safe, cost-effective, and easily measurable remains a significant challenge for researchers. In this article, we will explore the latest advancements in blood-based diagnostic biomarkers for CRC and their potential impact on improving patient survival rates.

Usefulness of machine learning and deep learning approaches in screening and early detection of breast cancer.

Breast cancer (BC) is one of the most common types of cancer in women, and its prevalence is on the rise. The diagnosis of this disease in the first steps can be highly challenging. Hence, early and rapid diagnosis of this disease in its early stages increases the likelihood of a patient's recovery and survival. This study presents a systematic and detailed analysis of the various ML approaches and mechanisms employed during the BC diagnosis process. Further, this study provides a comprehensive and accurate overview of techniques, approaches, challenges, solutions, and important concepts related to this process in order to provide healthcare professionals and technologists with a deeper understanding of new screening and diagnostic tools and approaches, as well as identify new challenges and popular approaches in this field. Therefore, this study has attempted to provide a comprehensive taxonomy of applying ML techniques to BC diagnosis, focusing on the data obtained from the clinical methods diagnosis. The taxonomy presented in this study has two major components. Clinical diagnostic methods such as MRI, mammography, and hybrid methods are presented in the first part of the taxonomy. The second part involves implementing machine learning approaches such as neural networks (NN), deep learning (DL), and hybrid on the dataset in the first part. Then, the taxonomy will be analyzed based on implementing ML approaches in clinical diagnosis methods. The findings of the study demonstrated that the approaches based on NN and DL are the most accurate and widely used models for BC diagnosis compared to other diagnostic techniques, and accuracy (ACC), sensitivity (SEN), and specificity (SPE) are the most commonly used performance evaluation criteria. Additionally, factors such as the advantages and disadvantages of using machine learning techniques, as well as the objectives of each research, separately for ML technology and BC detection, as well as evaluation criteria, are discussed in this study. Lastly, this study provides an overview of open and unresolved issues related to using ML for BC diagnosis, along with a proposal to resolve each issue to assist researchers and healthcare professionals.

Identification of molecular mechanisms causing skin lesions of cutaneous leishmaniasis using weighted gene coexpression network analysis (WGCNA).

Leishmaniasis is an infectious disease, caused by a protozoan parasite. Its most common form is cutaneous leishmaniasis, which leaves scars on exposed body parts from bites by infected female phlebotomine sandflies. Approximately 50% of cases of cutaneous leishmaniasis fail to respond to standard treatments, creating slow-healing wounds which cause permanent scars on the skin. We performed a joint bioinformatics analysis to identify differentially expressed genes (DEGs) in healthy skin biopsies and Leishmania cutaneous wounds. DEGs and WGCNA modules were analyzed based on the Gene Ontology function, and the Cytoscape software. Among almost 16,600 genes that had significant expression changes on the skin surrounding Leishmania wounds, WGCNA determined that one of the modules, with 456 genes, has the strongest correlation with the size of the wounds. Functional enrichment analysis indicated that this module includes three gene groups with significant expression changes. These produce tissue-damaging cytokines or disrupt the production and activation of collagen, fibrin proteins, and the extracellular matrix, causing skin wounds or preventing them from healing. The hub genes of these groups are OAS1, SERPINH1, and FBLN1 respectively. This information can provide new ways to deal with unwanted and harmful effects of cutaneous leishmaniasis.

Identification and validation of miR-583 and mir-877-5p as biomarkers in patients with breast cancer: an integrated experimental and bioinformatics research.

OBJECTIVES: Breast cancer (BC) is one of the most common cancers with a high mortality rate in women worldwide. The advantages of early cancer diagnosis are apparent, and it is a critical factor in increasing the patient's life and survival. According to mounting evidence, microRNAs (miRNAs) may be crucial regulators of critical biological processes. miRNA dysregulation has been linked to the beginning and progression of various human malignancies, including BC, and can operate as tumor suppressors or oncomiRs. This study aimed to identify novel miRNA biomarkers in BC tissues and non-tumor adjacent tissues of patients with BC. Microarray datasets GSE15852 and GSE42568 for differentially expressed genes (DEGs) and GSE45666, GSE57897, and GSE40525 for differentially expressed miRNAs (DEMs) retrieved from the Gene Expression Omnibus (GEO) database were analyzed using "R" software. A protein-protein interaction (PPI) network was created to identify the hub genes. MirNet, miRTarBase, and MirPathDB databases were used to predict DEMs targeted genes. Functional enrichment analysis was used to demonstrate the topmost classifications of molecular pathways. The prognostic capability of selected DEMs was evaluated through a Kaplan-Meier plot. Moreover, the specificity and sensitivity of detected miRNAs to discriminate BC from adjacent controls were assessed by area under the curve (AUC) using the ROC curve analysis. In the last phase of this study, gene expression on 100 BC tissues and 100 healthy adjacent tissues were analyzed and calculated by using the Real-Time PCR method. RESULTS: This study declared that miR-583 and miR-877-5p were downregulated in tumor samples in comparison to adjacent non-tumor samples (|logFC|< 0 and P ≤ 0.05). Accordingly, ROC curve analysis demonstrated the biomarker potential of miR-877-5p (AUC = 0.63) and miR-583 (AUC = 0.69). Our results showed that has-miR-583 and has-miR-877-5p could be potential biomarkers in BC.

Down-Regulation of circulating miR-23a-3p, miR-101-3p, and miR-let-7c in Women with Idiopathic Recurrent Pregnancy Loss.

BACKGROUND: Recently, circulating microRNAs have attracted much attention because they can serve as reliable, non-invasive diagnostic biomarkers for human diseases. This study aimed to quantify miR-23a-3p, miR-101-3p, and miR-let-7c expression levels in plasma samples of patients with idiopathic recurrent pregnancy loss (iRPL) and healthy subjects and to evaluate their potential diagnostic value in diagnosis of iRPL. METHODS: A total of 120 plasma samples were obtained from sixty women with a history of iRPL and sixty healthy fertile women to evaluate the expression levels of the circulating miR-23a-3p, miR-101-3p, and miR-let-7c by quantitative real-time polymerase chain reaction (qPCR) technique. The correlation between miR-23a-3p, miR-101-3p, and miR-let-7c and clinicopathological parameters was also assessed. Receiver operating characteristic (ROC) curve was plotted to determine the diagnostic accuracy of studied miRNAs in iRPL. RESULTS: Our results showed that the miR-23a-3p expression level in plasma of iRPL patients was lower than those in healthy controls but without a statistically significant difference (p = 0.113). The expression levels of miR-101-3p and miR-let-7c were significantly downregulated in iRPL patients compared with healthy subjects (p < 0.05). The plasma levels of miR-23a-3p and miR-let-7c were negatively correlated with number of abortions in iRPL patients. We observed statistically significant positive correlation between miR-23a-3p and miR-101-3p (r = 0.478, p = 0.001), miR-23a-3p and miR-let-7c (r = 0.561, p = 0.0001), and miR-101-3p and miR-let-7c (r = 0.533, p = 0.0001) in patients with iRPL. CONCLUSIONS: The current study provides evidence indicating that downregulation of miR-23a-3p, miR-101-3p, and miR-let-7c may be associated with iRPL.

Evaluation of the clinical significance of RNase III enzyme DROSHA in pediatrics acute lymphocytic leukemia.

Acute lymphocytic leukemia (ALL) is one of the subtypes of leukemia; it is one of the leading causes of malignancy and morbidity and childhood mortality. This study examined the dysregulation of DROSHA and its clinical implications in ALL. In the case-control investigation, we have included 140 samples, consisting of 70 peripheral whole blood samples diagnosed with ALL and 70 age and sex-matched healthy children, to assess the level of expression of DROSHA mRNA between two groups. Quantitative Real-Time PCR was used to establish the level of DROSHA gene expression in the patients and controls. The results revealed that DROSHA was overexpressed in patients compared with controls (p < 0.001). There were no major differences between DROSHA expression and demographic factors and clinicopathological parameters (p > 0.001). The finding of the study revealed that DROSHA expression in ALL patients is significantly up-regulated; which is suggesting that may be served as a critical role in the pathogenesis of ALL. Also, DROSHA will possibly be utilized as a novel therapeutic target for ALL patients within the future.

Analysis of clinical important of LncRNA-HOTAIR gene variations and ovarian cancer susceptibility.

LncRNAs are of functional long non-coding RNAs, which have been shown to be involved in critical pathways in cancer development. LncRNA-HOTAIR gene overexpression has been reported in several cancers. The aim of this study was to evaluate the associations between two variants of lncRNA-HOTAIR (rs1899663 G>T and rs4759314 A>G) gene polymorphisms and the risk of ovarian cancer (OC) susceptibility. We performed a case and control analysis on two hundred individuals consisting of 100 cases with OC and 100 women cancer-free in East Azerbaijan of Iranian population. To evaluate the association between two SNPs of lncRNA-HOTAIR with the risk of OC susceptibility used the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method. We revealed that two SNPs in the lncRNA-HOTAIR gene were significantly associated with the risk of OC. The dominant model of rs4759314 in lncRNA-HOTAIR (AA vs. GA/GG) showed a significantly increased risk with an OR of 10.036 (CI 2.253-44.712, P = 0.000); the recessive model of rs1899663 (TT vs. GT/GG) revealed a significantly increased risk with OR of 0.910 (CI 0.856-0.968; P = 0.002). In addition, our findings demonstrated that the 4759314G (OR 13.500; CI 3.146-57.940; P = 0.000) and 1899663T (OR 3.273; CI 1.433-7.475; P = 0.003) alleles are increased the risk of OC susceptibility. Our findings provide evidence that the specific genetic variants in lncRNA-HOTAIR gene may affect OC susceptibility in an Iranian population.

Negative associations between the has-miR-27a and hsa-miR-125a gene variations and prostate cancer susceptibility.

Micro-RNAs are a novel class of single-strand non-coding RNAs, which play an important role in tumorigenesis. This investigation aimed to evaluate associations between the hsa-miR-27a (rs895819 T > C) and hsa-miR-125a (rs12976445 C > T) gene variations and the risk of PCa. In the present case-control investigation, we have obtained 300 peripheral blood samples, consisting of 150 subjects with PCa and 150 healthy men. The genotype frequencies of hsa-miR-27a and hsa-miR-125a gene variations evaluated using the PCR-RFLP technique. Based on our findings, the genotype frequencies did not reveal a significant association between the rs895819T and rs12976445C variations and the risk of PCa in the three heredity models (P > 0.05). Minor alleles C and T of rs895819 and rs12976445 did not show an increased risk of PCa progression (P > 0.05). Our findings indicated that the hsa-miR-27a and hsa-miR-125a gene variations are not increased PCa predisposition in the Iranian population.

Clinical Application of Long Non-Coding RNA-UCA1 as a Candidate Gene in Progression of Esophageal Cancer.

Esophageal cancer (EC) is known as one of the most prevalent gastrointestinal cancers, and results in the seventh highest number of cancer-relevant deaths. Long non-coding RNAs (lncRNAs) have substantial roles in several biological processes. LncRNA human urothelial carcinoma associated 1 (UCA1) is announced to be enhanced in multiple types of human cancers. This survey was carried out to identify the potential role of the lncRNA-UCA1 in the progression of EC. A case-control investigation was performed on 140 FFPE tissues of EC patients consisting of 70 cancerous tissues and 70 marginal tissues samples. To determine the lncRNA-UCA1 gene expression changes, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) method was utilized. In addition, the associations between the lncRNA-UCA1 gene expression and clinicopathological parameters were assessed. Our findings revealed that the lncRNA-UCA1 was notably up-regulated in EC tissues compared to adjacent normal tissues (P < 0.05). LncRNA-UCA1 expression was substantially correlated to alcohol drinking (P = 0.008) and socioeconomic status (P = 0.001), while shared no correlation with age, hot drinking status and stage (P > 0.05). Our data indicated that the lncRNA-UCA1 play an important role in the progression of EC and may be considered as a candidate gene in the pathogenesis of EC patients.

Clinical important dysregulation of long non-coding RNA CCHE1 and HULC in carcinogenesis of cervical cancer.

Genetic analysis has revealed that the lncRNAs acted in the critical pathways including cell growth, cell differentiation, and tumorigenesis. The purpose of the present survey was to evaluate the lncRNA-CCHE1 and lncRNA-HULC expression variations in subjects with cervical malignancy. In our case-control analysis planned on 100 formalin-fixed paraffin-embedded (FFPE) samples comprising 50 paraffin blocks of cervical cancerous and 50 paraffin blocks of non-tumors samples. We have calculated the lncRNA-CCHE1 and lncRNA-HULC gene expression alterations using a quantitative RT-PCR approach. Our results declared that the lncRNA-CCHE1 expression was considerably raised in tumorous matched to the non-tumorous samples (P = 0.001). Moreover, the lncRNA-HULC expression was not considerably modified between tumorous samples matched to the non-tumorous samples (P = 0.060). In extension, lncRNA-CCHE1 expression variation was correlated with the histological type (P = 0.001), tumor size (P = 0.001) and FIGO stage (P = 0.001). Our data advised that the lncRNA-CCHE1 gene may influence cervical malignancy progression, held as a prognostic marker and useful curative target. However, the character of lncRNA-HULC in carcinogenesis of cervical malignancy requires further analyses.

Up-regulation of long non-coding RNA-PCAT-1 promotes invasion and metastasis in esophageal squamous cell carcinoma.

Long non-coding RNA prostate cancer associated transcript-1 ncRNA (lncRNA-PCAT-1) plays an important role in the progression of prostate cancer. The present investigation was aimed to evaluate the potential roles of the lncRNA-PCAT-1 gene expression changes in esophageal squamous cell carcinoma (ESCC) between Iranian population. In the case-control investigation, we have analyzed a total of 150 fresh tissue samples, compromising of 75 cancerous tissues and 75 adjacent normal tissues from patients with ESCC. We used quantitative Real-time polymerase chain reaction (qRT-PCR) to evaluate the lncRNA-PCAT-1 gene expression levels in ESCC patients and correlation between the lncRNA-PCAT-1 expression changes and clinical characteristics. Our findings showed that the lncRNA-PCAT-1 gene was up-regulated in cancerous tissues compared with the adjacent non-cancerous tissues (p=0.0016). In addition, the results revealed a significant correlation between up-regulating of lncRNA-PCAT-1 and hot liquid drinking (p =0.017). These findings offer the potential roles of lncRNA-PCAT-1 in the pathogenesis of ESCC and may consider as a candidate prognostic biomarker for ESCC in an Iranian population.

Nucleic acid vaccines for hepatitis B and C virus.

Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections accounts for an important global health problem affecting over 250 million people all around the world. They can cause acute, transient and chronic infections in the human liver. Chronic infection of liver can lead to its failure or cancer. To deal with this problem, alternative approaches or strategies to inhibit these infections have already been started. DNA and mRNA-based vaccination will increase the efficacy and reduce toxicity in patients with Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections. Gene vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development, low-cost manufacture and safe administration. MRNA-based vaccination is a method to elicit potent antigen-specific humoral and cell-mediated immune responses with a superior safety profile compared with DNA vaccines. Exploring the intricacies of these pathways can potentially help the researchers to explore newer vaccines. In this study, DNA and mRNA-based vaccination are introduced as an approach to treat Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections. DNA and mRNA-based vaccines as one of the most successful therapeutics are introduced and the clinical outcomes of their exploitation are explained.

Association of single nucleotide polymorphism in hsa-miR-499 and hsa-miR-196a2 with the risk of prostate cancer.

BACKGROUND: Prostate cancer (PCa) is one the most common malignant cancers in men. Micro-RNAs are a group of a noncoding small molecule, which plays critical roles in signalling pathways, metabolism, apoptosis and cancer development. The purpose of this study was to examine the possible association between the hsa-miR-499 (rs3746444) and hsa-miR-196a2 (rs11614913) gene polymorphisms with the risk of PCa. METHODS: The case-control investigation was performed on 300 peripheral blood samples, consisting of 150 patients with PCa and 150 healthy men without a family history of cancers. Genetic variations of hsa-miR-499 and hsa-miR-196a2 genes were assessed using the PCR-RFLP method. RESULTS: The T/T + TC/CC genotype frequencies showed a significant association between has-mir499 (rs3746444 T>C) gene polymorphism with the risk of PCa (p = 0.027; OR 1.780; 95% CI 1.030-3.113). The genotype frequencies of hsa-miR-196a2 gene did not reveal a statistically significant difference between two groups (p > 0.05). CONCLUSION: Our findings supported that hsa-miR-499 gene polymorphism significantly increased susceptibility to PCa and may be considered as a potential prognostic biomarker in PCa patients. The findings suggested that no correlation between hsa-miR-196a2 gene polymorphism and PCa susceptibility in an Iranian population.

Evaluation of clinical utility of P53 gene variations in repeated implantation failure.

Repeated implantation failure (RIF) is one the most common causes which showed during IVF (In vitro fertilization) procedure. We aim to evaluate the possibility role of nucleotide changes in rs1042522 (R72P; G/C) and rs17878362 (Ins16bp; N/D) of P53 gene in patients with RIF. In a case-control survey, we have considered 200 women, consisting of 100 cases with RIF and 100 women with the normal pregnancy. In order to determine the genotype frequencies, we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The NN + ND/DD (dominant) genotype frequencies of rs17878362 variant revealed a significant difference between two groups (P = 0.001; OR 2.652; 95% CI 1.480-4.754). In addition, the CC + GC/GG (recessive) genotype frequencies of rs1042522 (R72P) variant indicated a significant difference between two groups (P = 0.018; OR 3.353; 95% CI 1.169-9.616). Our findings suggested that rs1042522 (R72P; G/C) and rs17878362 (Ins16bp; N/D) of P53 gene polymorphisms could be a genetic predisposing factor for RIF.

Evaluation of prognostic usefulness of long noncoding RNA GAS5 and FAL1 in papillary thyroid carcinoma.

Genetic studies on cancers have revealed that lncRNA-GAS5 and lncRNA-FAL1 are overexpressed in some cancerous cells. The aim of the present investigation was to evaluate the roles of lncRNA-GAS5 and lncRNA-FAL1 gene expression changes in the diagnosis and prognosis of patients with papillary thyroid carcinoma (PTC). In a case-control investigation, we recruited a total of 140 formalin-fixed paraffin-embedded tissues of PTC, including 70 cancerous and noncancerous tissues. Quantitative real-time polymerase chain reaction was used to determine the lncRNA-GAS5 and lncRNA-FAL1 level of gene expression in the two tissue groups. The association between the clinicopathological characteristics of patients and the expression level of lncRNA-GAS5 and lncRNA-FAL1 was evaluated. Our findings revealed that the level of expression in the lncRNA-GAS5 and lncRNA-FAL1 genes was significantly upregulated in thyroid cancerous tissues (P < 0.003 and P < 0.040, respectively). The expression of lncRNA-GAS5 and lncRNA-FAL1 revealed a significant association with tumor node metastasis staging (P < 0.042 and P < 0.001, respectively). It seems that the lncRNA-GAS5 and lncRNA-FAL1 genes play an oncogenic role in PTC. The two genes have a significant potential prognostic value and may likely be used as novel therapeutic targets for PTC patients in the future.

Association of the study between LncRNA-H19 gene polymorphisms with the risk of breast cancer.

BACKGROUND: The H19 is a maternally expressed imprinted gene transcribing a long noncoding RNA (lncRNA), which has previously been reported to be involved in tumorigenesis and cancer progression. The aim of this study was to evaluate the associations between two lncRNA-H19 (rs3741219 T>C and rs217727 C>T) gene polymorphisms with the risk of breast cancer (BC). METHODS: In a case-control investigation, we evaluated 150 BC patients and 100 cancer-free subjects in East Azerbaijan Province of Iran. To assess two gene polymorphisms, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used. RESULTS: The genotype frequencies of two lncRNA-H19 (rs217727 C>T and rs3741219 T>C) gene polymorphisms TT + TC/CC and CC + CT/TT have not shown a statistically significant association with the risk of BC (P = 0.065; OR = 0.967; 95% CI, 0.938-0.996) and (P = 0.510; OR = 1.583; 95% CI, 0.399-6.726), respectively. In addition, our findings revealed a significant differences in allele frequencies in lncRNA-H19 rs217727 C>T polymorphism between groups (P = 0.033; OR = 1.985; 95% CI, 1.048-3.761). CONCLUSION: Our findings suggested that rs217727 C>T polymorphism may be involved in the pathogenesis of BC, whereas rs3741219 T>C variation may not be involved in the genetic background of BC in Iranian.

Long non-coding RNAs and cervical cancer.

Cervical cancer is determined as the second highest number of deaths factor in female cancers. Here is a need to find new biomarkers for detection and preliminary prognosis, metastasis. To find new treatment to enhance the survival of cervical cancer patients, pivotal actions are necessitated to be implemented. Long non-coding RNAs (lncRNAs) appear to be the crucial modulators in various processes and critically influence the oncogenesis. The commencement and general review actions of the following lncRNAs HOTAIR, H19, XIST, CCHE1, EBIC, MALAT1, ANRIL, LET, NEAT1, BLACAT1, UFC1, SNHG16 and SNHG20 are focused in this review article. Roles of the lncRNAs in cervical cancer in terms of prognosis and tumor progression, invasion and metastasis, apoptosis, and radio-resistance are pointed out. In this review the utilization of lncRNAs as biomarkers in cervical cancer prognosis for metastasis is discussed. An overview of this review will be useful for selection of biomarkers in diagnosis, prognosis, and targeted therapy of cervical cancer in the future.

Evaluation of the potential clinical prognostic value of lncRNA-BANCR gene in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the seventh most common cause of cancer death in worldwide. LncRNA-BANCR is a long non-coding RNA (lncRNA), which has made new windows in cancer investigations. The aim of this survey was to determine the lncRNA-BANCR gene expression changes in patients with ESCC. In case-control investigation was performed on 150 formalin fixed-paraffin embedded tissues (75 cancerous and 75 non-cancerous tissues) of ESCC patients. The lncRNA-BANCR gene expression alteration was assessed by Real-Time PCR technique. Our findings revealed that lncRNA-BANCR gene expression was increased significantly in tumor tissues compared with the non-cancerous tissues (p = 0.0025). In addition, lncRNA-BANCR gene expression changes was positively associated with the lymph node metastasis (p = 0.013), tumor differentiation (p = 0.019) and tumor stage (p = 0.017). Our results suggest a possible role of lncRNA-BANCR in proliferation of esophageal tissues and may be considered as a potential prognostic value for ESCC metastasis.

Molecular pathology diagnosis of diffuse large B cell lymphoma using BIOMED-2 clonal gene rearrangements.

BACKGROUND: Clonality testing for immunoglobulin gene rearrangement analysis could be implemented effectively as a useful technique for conventional diagnosis of lymphoma. The European Biomedicine and Health Concerted Action Project BMH4-CT98-3936 (BIOMED-2) have been suggested a gold standard method to clonality detection. OBJECTIVES: We tested empirically clonality rearrangements of IGH and incomplete IGH D-J, on formalin-fixed, paraffin embedded (FFPE) tissue of patients with diffuse large B cell lymphoma (DLBCL). MATERIAL AND METHODS: This appraisal was conveyed on 50 sequential FFPE specimens of patients with DLBCL. We carried out a standard multiplex PCR and heteroduplex techniques to analysis of IGH and incomplete IGH D-J clonal gene rearrangements. RESULTS: In our investigation, we were identified a total positive monoclonality of 96% (48/50) for IGH and 58% (29/50) for incomplete IGH D-J. The percentage of positive clonality was detected in three frameworks (FRI, II, III) of IGH revealed 50% (25/50), 28% (14/50) and 18% (9/50) to FRIII, FRII and FRI, respectively. Analysis of incomplete IGH D-J showed 34% (17/50) and 24% (12/50) rates of positive clonality for DH1-6-JH and DH7-JH, respectively. In the 4% (2/50) of cases was no detected any gene rearrangements in both of IGH and incomplete IGH D-J genes. CONCLUSIONS: Analysis of molecular clonality gene rearrangements on FFPE tissues disclosed that using BIOMED-2 protocols, could be improvement significant clinicopathological diagnosis of DLBCL. Clonality testing is believable that to suggest as a helpful and credible technique for clonality detection in the routine diagnosis of DLBCL and other lymphoproliferative disorders.

Clinical Applications of Next-Generation Sequencing in Cancer Diagnosis.

With the advancement and improvement of new sequencing technology, next-generation sequencing (NGS) has been applied increasingly in cancer genomics research fields. More recently, NGS has been adopted in clinical oncology to advance personalized treatment of cancer. NGS is utilized to novel diagnostic and rare cancer mutations, detection of translocations, inversions, insertions and deletions, detection of copy number variants, detect familial cancer mutation carriers, provide the molecular rationale for appropriate targeted, therapeutic and prognostic. NGS holds many advantages, such as the ability to fully sequence all types of mutations for a large number of genes (hundreds to thousands) and the sensitivity, speed in a single test at a relatively low cost compared to be other sequencing modalities. Here we described the technology, methods and applications that can be immediately considered and some of the challenges that lie ahead.