The molecular genetic profile of neuroblastoma

2014 ◽  
Vol 20 (2) ◽  
pp. 76-83 ◽  
Author(s):  
Paul Scott Thorner
Keyword(s):  
Molecular Genetic ◽  
Genetic Profile

PREDICTIVE VALUE OF THE DYNAMIC DETERMINATION OF CIRCULATING TUMOR DNA ON PFS IN PATIENTS WITH EGFR MUTATED NSCLC, WITH OSIMERTINIB THERAPY

2020 ◽  
Vol 66 (2) ◽  
pp. 135-142
Author(s):  
Fedor Moiseenko ◽  
Mariya Stepanova ◽  
Nikita Volkov ◽  
Albina Zhabina ◽  
A. Myslik ◽  
...  
Keyword(s):  
Predictive Value ◽  
Molecular Genetic ◽  
Predictive Marker ◽  
Circulating Tumor Dna ◽  
Qualitative Assessment ◽  
Genetic Profile ◽  
T790m Mutation ◽  
Rare Mutations ◽  
Effect Of Therapy ◽  
Pcr Method

Aim: study of the predictive value of determining ctDNA during treatment with osimertinib in patients with NSCLC with EGFR mutation. Methods: The study included patients with metastatic EG-FR-associated NSCLC, in whom, with progression against the background of 1st - 2nd generation TKIs, the T790M mutation was detected. Patients received osimertinib therapy 80 mg/ day, daily, until progression. Before treatment, and then every 2 months, whole blood was taken to conduct a qualitative assessment of ctDNA in dynamics by the RT-PCR method. Results: From 2016 to 2019 in St. Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Care (Oncology), 22 patients were identified T790M associated progression of EGFR NSCLC. 81.9% (18/22) are women, 18.1% (4/22) are men. The average age is 61.2 years (50-75). 1/22 had smoking experience for more than 30 years. The molecular genetic profile in 16 is represented by ex19del, 5 L858R, 1 -a combination of rare mutations G719S+S768I. The effect of therapy was evaluated in 20/22 patients. PR and SD were registered in 9/20 (45%) and 10/20 (50%) patients, respectively. Median PFS - 16.7 months (cI 95%, 11,4-22,0). In 12/22 patients was observed the disappearance of ctDNA T790M after 2 months of osimertinib therapy. PFS is 18,9 months (95% CI, 14,8-19,7), in patients with no mutation detected in the second month of treatment compared with the group of patients in which the ctDNA was determined (PFS 8.0 months) (CI 95%, 4,2-11,8) (p=0.015). Correlation analysis did not reveal any clinical factors associated with the disappearance of ctDNA. Conclusions: The disappearance of ctDNA in plasma after 2 months of treatment with osimertinib is associated with an increase in PFS and can be considered as a predictive marker in patients with metastatic NSCLC EGFR T790M.

scholarly journals ETIOTROPIC THERAPY FOR DIFFERENT FORMS OF HEPATITIS B

2021 ◽  
Vol 5 (1) ◽  
pp. 50-55
Author(s):  
E. N. Priima ◽  
◽  
A. D. Bushmanova ◽  
K. E. Novak ◽  
E. V. Esaulenko ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Clinical Laboratory ◽  
Molecular Genetic ◽  
Genetic Profile ◽  
B Virus ◽  
Hbsag Seroconversion

Background. Currently, etiotropic therapy of hepatitis B in most cases is carried out using nucleot(s)ide analogues. The ultimate goal of the therapy depends on the period of its administration – in acute or chronic hepatitis. The influence of the molecular genetic profile of the hepatitis B virus on the effectiveness of therapy in both acute and chronic forms of the disease has not yet been established, which requires further research. Objective. To assess the possibilities of modern etiotropic therapy in acute and chronic forms of hepatitis B. Material and methods. The article analyzes the indicators of clinical, laboratory and instrumental data of patients who received etiotropic therapy with nucleot(s)ide analogues. Results. Etiotropic therapy resulted in a viral load decrease to an undetectable level in all patients regardless of the course of hepatitis B and infection with either a "mutant" or "wild" virus strain. In acute hepatitis B, HBV DNA was not detected in 100% of cases after 24 weeks of therapy, in HBsAg seroconversion - after 36 weeks; in chronic hepatitis B - after 36 weeks without HBsAg seroconversion. Six months after the completion of the treatment, the patients with chronic hepatitis B developed relapse in 89.7% of cases, but the viral load was less than 2000 IU / ml, and the severity of liver fibrosis was insignificant. In the rest of the cases, resumption of therapy was required. Conclusions. It was found that mutations of the hepatitis B virus do not affect the effectiveness of etiotropic therapy. The rate of viral load decrease correlates with the form of hepatitis B and is significantly higher in acute disease.

scholarly journals Molecular and biological characteristics of keratin intermediate filaments in intact skin under systemic inflammation

2020 ◽  
pp. 34-39
Author(s):  
Г.А. Демяшкин ◽  
Е.Ю. Шаповалова ◽  
М.Ю. Маланичев ◽  
Д.А. Погосян ◽  
М.А. Батов ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Molecular Genetic ◽  
Skin Barrier ◽  
Keratinocyte Differentiation ◽  
Critical Conditions ◽  
Genetic Profile ◽  
Intact Skin ◽  
Keratinocyte Proliferation ◽  
Expression Of Genes ◽  
And Migration

Введение. Несмотря на определенный прогресс в изучении патоморфологических механизмов сепсиса и усовершенствовании методов терапии критических состояний, летальность при сепсисе сохраняется на высоком уровне. При тяжелом системном воспалении нарушается морфофункциональное состояние кожного покрова, однако обусловливающие этот эффект механизмы описаны поверхностно. Нуждается в уточнении роль изменения экспрессии генов кератиноцитов цитоскелета, приводящая к нарушению их дифференцировки и миграции на фоне действия эндогенного фактора, индуцированного тяжелым системным воспалением. Цель работы - оценка молекулярно-генетического профиля дифференцировки и миграции кератиноцитов на фоне системного воспаления. Методика. Фрагменты интактной кожи пациентов с подтвержденным сепсисом (n=46) были изучены методом полимеразной цепной реакции в режиме реального времени для определения экспрессии генов промежуточных филаментов кератиноцитов KRT1, KRT10, KRT5, KRT14 и KRT16. Результаты. У пациентов в условии системного воспаления относительная экспрессия KRT1, KRT10, KRT5, KRT14 и KRT16 в интактной коже снижена, несмотря на сохранение уровня экспрессии генов, продукты которых поддерживают агрегацию филаментов и стабильность цитоскелета - FLG, IVL. Заключение. В интактной коже на фоне системного воспаления в отсутствие внешнего повреждающего фактора отмечается разобщение дифференцировки и пролиферации кератиноцитов, способное привести к нарушению барьерной функции кожи. Introduction. Despite some progress in studying pathomorphological mechanisms of sepsis and improvement of therapy for critical conditions, mortality in sepsis remains high. In severe systemic inflammation, the morpho-functional state of skin is compromised; however, the mechanisms responsible for this effect are not completely understood. The role of mutations in keratinocyte cytoskeletal genes leading to disorders of keratinocyte differentiation and migration under the action of an endogenous factor induced by severe systemic inflammation, needs to be clarified. The aim of this work was to assess the molecular genetic profile of keratinocyte differentiation and migration under systemic inflammation. Methods. Fragments of intact skin from patients with confirmed sepsis (n=46) were studied with real-time polymerase chain reaction to determine the expression of keratin intermediate filament KRT1, KRT10, KRT5, KRT14, and KRT16 genes. Results. In patients with systemic inflammation, the relative expression of KRT1, KRT10, KRT5, KRT14, and KRT16 in intact skin was reduced, despite the normal expression of genes whose products support filament aggregation and cytoskeletal stability (FLG and IVL). Conclusion. In the intact skin under systemic inflammation in the absence of an external damaging factor, uncoupling of the keratinocyte differentiation from the keratinocyte proliferation was observed, which may lead to dysfunction of the skin barrier.

2908 Changes of a molecular genetic profile in the neuroepithelial tumors in the brain after their malignant transformation

2015 ◽  
Vol 51 ◽  
pp. S587
Author(s):  
M. Matsko ◽  
D.E. Matsko ◽  
A.Y. Ulitin ◽  
A.G. Ievleva ◽  
N.M. Volkov ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Molecular Genetic ◽  
Genetic Profile ◽  
Neuroepithelial Tumors ◽  
The Brain

scholarly journals DNA Identification from Sebaceous Sweat Fingerprint Deposits on Corpse Integuments

2018 ◽  
Vol 13 (2) ◽  
pp. 97-104
Author(s):  
Tat’yana G. Faleeva ◽  
Igor’ V. Kornienko ◽  
Igor’ N. Ivanov ◽  
Semen M. Kuz’menko ◽  
Evgenii S. Mishin ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Skin Surface ◽  
Genetic Profile ◽  
Dna Identification ◽  
Molecular Genetic Study ◽  
Oil Residue ◽  
Specific Allele ◽  
Significant Temperature ◽  
Chromosomal Loci ◽  
Poor Adhesion

The paper presents the results of a pilot molecular genetic study of sweat and oil residue left by the fingertips and hand palms of male volunteers (donors) on various regions of the skin surface of dead bodies (recipients) of both sexes. In cases of contact with female recipients donor-specific allele combinations were obtained for only 11.6% of autosomal loci and 12.9% of Y-chromosomal loci. Donor-specific traits were absent in 68.4% of autosomal loci and 87.1% of Y-chromosomal loci. In cases of contact with male recipients the full genetic profile was obtained for 18.6% of autosomal loci, and 64.2% of loci showed a lack of donor-specific alleles. Meanwhile, allelic combinations specific to female recipients were encountered in 40.5% of autosomal loci, and to male recipients – in 34.2% of autosomal loci. Results demonstrate poor adhesion of sweat and oil compounds from donors’ hands to the corpses’ skin, probably due to significant temperature differences between contact surfaces. 

scholarly journals Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman

2020 ◽  
Author(s):  
Intisar Al Alawi ◽  
Elisa Molinari ◽  
Issa Al Salmi ◽  
Fatma Al Rahbi ◽  
Adhra Al Mawali ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Clinical Diagnosis ◽  
Autosomal Recessive ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Pcr Analysis ◽  
Genetic Profile ◽  
Polycystic Kidney ◽  
Genetic Characteristics

Abstract Background There is a high prevalence of rare genetic disorders in the Middle East, and their study provides unique clinical and genetic insights. Autosomal recessive polycystic kidney disease (ARPKD) is one of the leading causes of kidney and liver-associated morbidity and mortality in Oman. We describe the clinical and genetic profile of cohort of ARPKD patients.Methods We studied patients with a clinical diagnosis of ARPKD ( n =40) and their relatives [parents ( n =24) and unaffected siblings ( n =10)] from 32 apparently unrelated families, who were referred to the National Genetic Centre in Oman between January 2015 and December 2018. Genetic analysis of PKHD1 was performed through next generation sequencing (NGS) and Sanger sequencing.Results A clinical diagnosis of ARPKD was made prenatally in 8 patients, 21 were diagnosed during infancy (0-1 year), 9 during early childhood (2-8 years) and 2 at later ages (9-13 years). Clinical phenotypes included polycystic kidneys, hypertension, hepatic fibrosis and splenomegaly. 24 patients had documented chronic kidney disease. 24 out of the 32 families had a family history suggesting an autosomal recessive pattern of inherited kidney disease, and there was known consanguinity in 21 families (66%). A molecular genetic diagnosis with biallelic PKHD1 mutations was confirmed in 38 patients from 30 different families, giving a detection rate of 94%. Two unrelated patients remained genetically unsolved. In all of the solved cases, only four different PKHD1 missense pathogenic variants were identified: c.107C>T, p.(Thr36Met); c.406A>G, p.(Thr136Ala); c.4870C>T, p.(Arg1624Trp) and c.9370C>T, p.(His3124Tyr) located in exons 3, 6, 32 and 58, respectively. The c.406A>G, p.(Thr136Ala) missense mutation was detected homozygously in one family and heterozygously with a c.107C>T, p.(Thr36Met) allele in 5 other families. Overall, the most commonly detected pathogenic allele was c.107C>T; (Thr36Met), which was seen in 24 families.Conclusion Molecular genetic screening of PKHD1 in clinically suspected ARPKD cases produced a high diagnostic rate. The four PKHD1 missense variants identified suggest there may be common founder alleles in the Omani population. Cost effective targeted PCR analysis of these specific alleles can be a useful diagnostic tool for future cases of suspected ARPKD in Oman.

scholarly journals Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman

2020 ◽  
Author(s):  
Intisar Al Alawi ◽  
Elisa Molinari ◽  
Issa Al Salmi ◽  
Fatma Al Rahbi ◽  
Adhra Al Mawali ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Clinical Diagnosis ◽  
Autosomal Recessive ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Pcr Analysis ◽  
Genetic Profile ◽  
Polycystic Kidney ◽  
Genetic Characteristics

Abstract Background: There is a high prevalence of rare genetic disorders in the Middle East, and their study provides unique clinical and genetic insights. Autosomal recessive polycystic kidney disease (ARPKD) is one of the leading causes of kidney and liver-associated morbidity and mortality in Oman. We describe the clinical and genetic profile of cohort of ARPKD patients. Methods: We studied patients with a clinical diagnosis of ARPKD (n=40) and their relatives (parents (n=24) and unaffected siblings (n=10)) from 32 apparently unrelated families, who were referred to the National Genetic Centre in Oman between January 2015 and December 2018. Genetic analysis of PKHD1 if not previously known was performed using targeted exon PCR of known disease alleles and Sanger sequencing. Results: A clinical diagnosis of ARPKD was made prenatally in 8 patients, 21 were diagnosed during infancy (0-1 year), 9 during early childhood (2-8 years) and 2 at later ages (9-13 years). Clinical phenotypes included polycystic kidneys, hypertension, hepatic fibrosis and splenomegaly. 24 patients had documented chronic kidney disease (median age 3 years). 24 out of the 32 families had a family history suggesting an autosomal recessive pattern of inherited kidney disease, and there was known consanguinity in 21 families (66%). A molecular genetic diagnosis with biallelic PKHD1 mutations was known in 18 patients and newly identified in 20 other patients, totalling 38 patients from 30 different families. Two unrelated patients remained genetically unsolved. The different PKHD1 missense pathogenic variants were: c.107C>T, p.(Thr36Met); c.406A>G, p.(Thr136Ala); c.4870C>T, p.(Arg1624Trp) and c.9370C>T, p.(His3124Tyr) located in exons 3, 6, 32 and 58, respectively. The c.406A>G, p.(Thr136Ala) missense mutation was detected homozygously in one family and heterozygously with a c.107C>T, p.(Thr36Met) allele in 5 other families. Overall, the most commonly detected pathogenic allele was c.107C>T; (Thr36Met), which was seen in 24 families. Conclusions: Molecular genetic screening of PKHD1 in clinically suspected ARPKD cases produced a high diagnostic rate. The limited number of PKHD1 missense variants identified in ARPKD cases suggests these may be common founder alleles in the Omani population. Cost effective targeted PCR analysis of these specific alleles can be a useful diagnostic tool for future cases of suspected ARPKD in Oman.

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