Medicina Molecular e Genética

Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide and the second leading cause of cancer-related deaths. Adenocarcinoma accounts for approximately 95% of all malignant gastric neoplasms. Most localized GC (stages II and III) are best treated with multimodality therapy with a 5-year survival in approximately 40% of patients; however, advanced GC only has limited treatment options with poor prognosis. GC is a highly heterogenous disease. Historically, many classification systems have been proposed, including anatomical classification (Borrmann classification, Siewert and Stein classification), histological classification (WHO classification, Laurén’s classification), and extent of disease (early gastric cancer vs. advanced cancer). Originally proposed in 1965, the Laurén’s classification divides GC into intestinal- and diffuse-types that are quite distinct in the histological features, epidemiology, and etiology.

We present the case of a 45-year-old woman admitted to our hospital with acute heart failure and cardiogenic shock requiring stabilization with an intra-aortic balloon pump, inotropes and vasopressors. Nevertheless, the patient developed a multi organ failure. Firstly, diagnosed as an acute myocarditis, bilateral pheochromocytoma was discovered with MRI scan and confirmed with urine and plasma metanephrines. Bilateral adrenalectomy was performed. The genetic testing revealed a mutation in the Neurofibromatosis type 1 gene. Given the life-threatening complications and the good prognosis after radical surgery, the diagnosis of pheochromocytoma should be quickly considered in patients presenting with unexplained cardiovascular compromise.

All characteristics of genomes such as their structure, method of evolution and arrangement are covered in genomics. This science includes a complete DNA double strand which covers all DNA genes. Genetic is completely different from genomics where genetic is dealing with individual gene and its role in heritage while genomics covers quantification and qualification of genes which incorporates in protein production. This review aims to discuss in detail the role of genomics application in different medical fields such as genomic medicine, medical biotechnology, molecular medicine, biomedical engineering, medical anthropology, social medicine, conservative medicine and pharmacology and biomarkers discovery. Genomics controls social life around the world in research and health. Genomics helps to understand ourselves as individuals and as members of the family or society. Genomics is the investigation of an organism's genomics at the functional condition of various parts that cover the blueprint of the living cell to reveal the physiology of the cell and its basic, developmental, and tissue-specific processes. Genomics new techniques measure the behaviour of genes inside the cell as well as the analysis and the management of biological data and this concept plays a major role in recent molecular biology. Genomics used also to develop the next generation of antimicrobials against harmful strains of bacteria and viruses. Genomics gives a map about the biological cells under physiologic and pathologic conditions which help in the progress of disease diagnosis, therapy and drug development. The biomedical engineering reproduces the recent progress in genomics arrangement data which leads to the huge progress in drug detection, biomarkers discovery and disease treatment. Consequently, future genomics researches are the basis for detecting the initiation of many human diseases which help in therapy advances in the future.

Accurate quantification of HIV-1 viral load (VL) is crucial for assessing infection stage and efficacy of antiretroviral therapy (ART). Despite recommendations for measuring VL amongst people living with HIV, the accessibility and availability of this parameter remain low in resource-limited settings, primarily due to the lack of qualified human resources and necessary reagents. Solutions must be found to help developing countries attain the Joint United Nations Program on HIV/AIDS (UNAIDS) 90-90-90 targets for 2020. This study was designed to compare the quantification of HIV-1 VL between two reverse transcriptase real-time PCR techniques: RocheCOBAS^® AmpliPrep/ COBAS^®TaqMan^®HIV-1v2.0 and Abbott m2000sp/m2000rt. To conduct the comparison, 231 samples for VL were assessed. Samples were stratified according to the following VL intervals:<3 Log10; 3 Log10-4 Log10; 4 Log-5 Log10; 5 Log10-6 Log10 and > 6 Log10 copies/ml. The Bland-Altman method and the Bland-Altman plot were used for the comparison of the two techniques. The concordance varies from 92 to 98% depending on the VL interval studied. Our results showed that these two techniques give similar results and that all observed variations are under 0.5 Log10 copies/ml, which is considered a significant variation for treatment failure. This concordance was confirmed by the overall VL comparison obtained using linear regression. The linear regression shows a correlation with R² = 0.83 and a 95% agreement between the two techniques. Our results show that these techniques are interchangeable and thus, in some contexts, would improve the availability of VL to help achieve the UNAIDS third "90" target set for 2020.

Aim: We investigated the patient and tumor characteristics of breast cancer patients with a high familial risk. The families in which the standard genetic testing revealed a BRCA1 or BRCA2 mutation were excluded to identify clinical characteristics that can be linked with an unknown genetic mutation. These characteristics were compared with those from patients in the same cohort in whom a mutation was found in BRCA1 or BRCA2 and to those from sporadic breast cancer cases (Belgian cancer registry).

Methods: The files of familial cancer cases that underwent BRCA1/2 testing between 1994 and 2012 were retrospectively analyzed.

Results: The BRCA1 related breast cancers occur at a median age of 42, BRCA2 at a median age of 44, familial non-BRCA1/2 at a median age of 47 and sporadic breast cancer at the age of 63. The lower median age of incidence in the non-BRCA1/2 group compared to the sporadic breast cancer group makes use conclude that there are probably moderate risk genes involved. Generational anticipation was also observed in some of the BRCA1/2 negative families. We did not find any significant differences in the pathological characteristics of breast cancers occurring in BRCA1/2 negative patients with a high familial risk compared to sporadic cases.

Conclusion: A shift towards a younger age of disease incidence and “anticipation” in some families suggests the involvement of a genetic factor. The identification of other genetic causes in these familial cases is therefore warranted.

Cancer is a group of diseases that are characterized by the development of abnormal cells, which divide almost without limit, develop, spread without control anywhere in the body, losing the cells their ability to disappear by an anti- apoptotic action, essential process for malignant transformation and tumor development. The onset and development of cancer is associated with multiple causes and predisposing factors such as stress and psychosocial factors PAI-1 is a gene regulated by stress and is paradoxicallyinteracted in close relation with uPA in the development of tumors.

Isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) mutations are frequent in acute myeloid leukemia (AML). Here we describe the qualitative polymerase chain reaction (PCR)-based Abbott Realtime IDH1 and IDH2 assays, which detect single nucleotide variants coding for five IDH1 and nine IDH2 mutations. We evaluated the sensitivity and specificity of the Abbott Real-Time IDH1/IDH2 assays and conducted a workflow analysis that compared them with PCR-based Sanger and next-generation sequencing (NGS) assays in blood or bone marrow specimens from 100 AML patients. Sanger sequencing and NGS detected IDH mutations with variant allele sensitivity limits of 20% and 10%, respectively. The Abbott Real-Time IDH1/IDH2 assays demonstrated 100% sensitivity and 95% specificity vs. Sanger sequencing and detected mutations at the 1% level. Low-level IDH2 mutations in five samples were detected by the Abbott Real-Time IDH2 assay but not by Sanger sequencing. Turnaround time (TAT) based on a workflow analysis showed Abbott Real-Time IDH1/IDH2 assay results were available in three business days vs. eight days for Sanger sequencing and 15 days for NGS. Higher sensitivity and rapid TAT for detecting IDH mutations may improve identification of patients with lower mutant-IDH burden and allow for quicker administration of the FDA-approved IDH inhibitors, Ivosidenib and Enasidenib.

In today’s era, AIDS (Acquired immune deficiency syndrome) has been changed from a death sentence to a manageable chronic disease after usage of antiretroviral therapy (ART). Although, according to NACO 2015 and UNAIDS 2017, there was a 54% decline in AIDS death from 2007 to 2015 and an overall 32% decline in new HIV infection (80,000 in 2016). It is still one of the leading causes of death. UNAIDS (2017) reported 2.1 million (1.324 billion) people living with HIV in India and with a ranked third in the world.

Control of myeloid differentiation and leukemia stem cell (LSC) self-renewal involves genetic and epigenetic regulators and mechanisms. Genetic regulation in leukemia has been highlighted as a novel way for maintaining the LSC program. Translocations of histone methyltransferases, such as the mixed-lineage leukemia (MLL) genes including Hoxa9, Myc, and Ikzf2, give rise to one of the most aggressive subtypes of acute myeloid leukemia (AML). Uncontrolled expansion of immature myeloid cells coupled with leukemia stem cell self-renewal and a block in differentiation are some of the characteristic traits of AML.

Background: Gaucher disease is a rare multi-systemic metabolic disorder resulting from the deficiency in β-glucocerebrosidase enzyme, with consequent accumulation of glucocerebroside. Less than 15% of mean normal activity β-glucocerebrosidase in leukocytes is the gold standard for the diagnosis of Gaucher disease, which is supplemented by a massive elevation in chitotriosidase enzyme activity. We report here our experience in the biochemical diagnosis of Gaucher disease by showing the variability and the heterogeneity of the activity of enzymes over 25 years from 1993-2017, through referring 5128 clinically suspected Gaucher disease cases to our Biochemical Genetics Department, National Research Centre, as the main reference lab in Egypt for the diagnosis of Inherited Metabolic Disorders.

Methods: β-glucosidase enzyme activity and chitotriosidase were done to all referred cases. Sphinogmylinase activity was estimated for all cases with normal activity of β- glucosidase and moderate elevation of chitotriosidase.

Results: Out of the 5128 suspected cases, 881 (17%) had deficiency in β-glucocerebrosidase activity, accompanied with high chitotriosidase activity level, ranges (213-66700 μmol/l/h) and mean (7254.8 μmol/l/h). Zero chitotriosidase activity is found in 9 patients (1%) with low β-glucosidase. 451 cases were diagnosed as Niemann Pick patients (8.8%).

Discussion and Conclusion: Other biochemical markers are needed in addition to chitotriosidase enzyme for the diagnosis. Molecular testing was done in relatively small numbers and need to be available parallel with biochemical testing.

Spitz neoplasms are relatively uncommon melanocytic lesions characterized by an epithelioid or spindled cell morphology and present more commonly in younger age. They represent a spectrum from benign to malignant lesions which sometime represent a diagnostic conundrum. Recent advances in the genetic characterization of these lesions allow a better classification with consequent improvement in diagnostic accuracy and patient management. This review aims at summarizing our recent understanding of these lesions at the molecular level.