scholarly journals Clinician's modern approaches to molecular genetic diagnosis of glioblastomas

2021 ◽  
Vol 67 (1) ◽  
pp. 13-19
Author(s):  
Turna Ashkhatcava ◽  
Marina Tatarinova ◽  
Lali Kogoniya ◽  
David Naskhletashvili ◽  
Vadim Zhukov
Keyword(s):  
Braf Mutation ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Braf V600e ◽  
Poor Prognostic Factor ◽  
Molecular Genetic Diagnosis ◽  
The Brain ◽  
Tert Mutation ◽  
Primary Glioblastomas

The article is devoted to the issue of molecular genetic diagnosis of cerebral glioblastomas. Despite significant advances in neurooncology, little progress has been made in prolonging the life of patients with cerebral glioblastoma, and a significant part of the effectiveness of treatment depends on the recognition of two prognostic biomarkers: mutations of the isocitrate dehydrogenase (IDH) promoter and  the methylation of the O6-methylguanine methyl transferase (MGMT) promoter. The article summarizes the data of world and domestic clinical studies, allowing to supplement the histological characteristics of primary glioblastomas with genetic markers: the presence of the TERT mutation, EFGR amplification, loss of PTEN function, LOH 10q, and the presence of the BRAF mutation. It should be noted that the amplification of EGFR, causing resistance to apoptotic stimuli and alkylating chemotherapy with Temozolomide, attracts much attention as a therapeutic target. The frequency of occurrence of the TERT mutation is 90% of all tumors of various genesis, most often the TERT mutation is found in oligodendroglioma or primary glioblastoma. Loss of heterozygosity in the region of localization of the PTEN gene is observed in many types of sporadic tumors, including more than 40% of glioblastomas. Mutations in this gene are found in tumors of the brain, endometrium, prostate, kidney, and mammary gland. The presence of a PTEN mutation is a poor prognostic factor. LOH 22q is much more common in secondary glioblastomas (82%) than in primary glioblastomas (41%). Among brain tumors, the BRAF mutation is most common with pleomorphic xanastrocytoma (60-70%).The BRAF V600E mutation was found in epithelioid glioblastoma, which is a rare and aggressive type of glioblastoma, characterized by an unfavorable prognosis (about 6 months) and frequent leptomeningeal spread. Thus, knowledge of the molecular mechanisms of carcinogenesis will enable a personalized approach to treatment with glioblastomas of the brain.

Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism

2020 ◽  
Vol 33 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Tatsushi Tanaka ◽  
Kohei Aoyama ◽  
Atsushi Suzuki ◽  
Shinji Saitoh ◽  
Haruo Mizuno
Keyword(s):  
Congenital Hypothyroidism ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Japanese Patients ◽  
Thyroid Stimulating Hormone ◽  
Allelic Variant ◽  
Genetic Investigation ◽  
Pathogenic Variants ◽  
Recessive Genes ◽  
Molecular Genetic Diagnosis

AbstractObjectivesCongenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations.MethodsWe enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH.ResultsWe identified potentially pathogenic bi-allelic variants in DUOX2, TSHR, and TPO in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in NKX2-1 (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (DUOX2, TSHR, TG, DUOXA2, and TPO) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic DUOX2 variants showed a more severe clinical presentation in infancy than those with bi-allelic TSHR variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic DUOX2 variants.ConclusionsThe prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.

Mitochondrial encephalopathies: molecular genetic diagnosis from blood samples

The Lancet ◽  
1991 ◽  
Vol 337 (8753) ◽  
pp. 1311-1313 ◽  
Author(s):  
S.R. Hammans ◽  
M.G. Sweeney ◽  
M. Brockington ◽  
J.A. Morgan-Hughes ◽  
A.E. Harding
Keyword(s):  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Blood Samples ◽  
Molecular Genetic Diagnosis

scholarly journals RARE-36. DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMORS: A REVIEW OF CLINICAL AND MOLECULAR CHARACTERISTICS, AND OUTCOME IN A PEDIATRIC POPULATION AT A SINGLE CENTER

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii450-iii450
Author(s):  
Valerie Cruz Flores ◽  
Thomas Geller ◽  
Ignacio Gonzalez Gomez ◽  
Luis Rodriguez ◽  
Javier Quintana ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Pediatric Population ◽  
Molecular Genetic ◽  
Intractable Epilepsy ◽  
Retrospective Chart Review ◽  
Braf V600e ◽  
Molecular Characteristics ◽  
Dysembryoplastic Neuroepithelial Tumor ◽  
Free Standing ◽  
Presenting Symptoms

Abstract BACKGROUND Neuronal and mixed neuro-glial tumors of the central nervous system (CNS) are relatively rare. Dysembryoplastic neuroepithelial tumor (DNET) is a benign, rare, slow-growing tumor, but in many cases is associated with intractable epilepsy. OBJECTIVE To report the experience with DNET at a single free-standing children’s institution. METHODS A retrospective chart review of 24 patients with confirmed DNET between 2001 and 2019 was performed. Data was collected on clinical characteristics, tumor location, surgical management, histopathological and molecular findings, and outcomes. RESULTS Mean age at diagnosis was 10 years (range 2 to 19 years), with female predominance (54.2%). Most common presenting symptoms were seizures (79.2%) and headaches (12.5%). Location of the tumor was temporal (29.2%), frontal (25.0%), parietal (16.7%), cerebellar (12.5%) and occipital (4.2%). A gross total resection was achieved in half the cases. Recurrence occurred in 4 patients (16.7%), all of whom had subtotal resections. The average follow up since diagnosis was 4.6 years (range 0.3 to 14 years). Nineteen patients presented with seizures, of which 63.2% were seizure free after surgery. The samples with molecular genetic testing (microarrays or FISH), were all normal except one patient positive for BRAF V600E mutation. CONCLUSIONS This is the first and largest review of pediatric DNETs in the last 10 years. Despite majority of patients having a favorable outcome after surgery, a subset of patients remains symptomatic. As molecular mechanisms in DNET remain unknown, future aim is to describe the molecular characteristics of our DNET population, and correlate with outcomes.

scholarly journals Molecular Genetic Diagnosis of von Hippel-Lindau Disease: Analysis of Five Japanese Families

1996 ◽  
Vol 87 (5) ◽  
pp. 423-428 ◽  
Author(s):  
Hiroshi Kanno ◽  
Taro Shuin ◽  
Keiichi Kondo ◽  
Susumu Ito ◽  
Masahiko Hosaka ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease ◽  
Molecular Genetic Diagnosis ◽  
Disease Analysis

scholarly journals Efficient Molecular Genetic Diagnosis of Enlarged Vestibular Aqueducts in East Asians

2009 ◽  
Vol 13 (5) ◽  
pp. 679-687 ◽  
Author(s):  
Byung Yoon Choi ◽  
Andrew K. Stewart ◽  
Katherine K. Nishimura ◽  
Won Jae Cha ◽  
Moon-Woo Seong ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
East Asians ◽  
Molecular Genetic Diagnosis
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