scholarly journals Adult-onset hyperinsulinaemic hypoglycaemia in clinical practice: diagnosis, aetiology and management

2017 ◽  
Vol 6 (7) ◽  
pp. 540-548 ◽  
Author(s):  
Benjamin G Challis ◽  
Andrew S Powlson ◽  
Ruth T Casey ◽  
Carla Pearson ◽  
Brian Y Lam ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Somatic Mutation ◽  
Metastatic Disease ◽  
Stage Iv ◽  
Stage I ◽  
Adult Onset ◽  
Hyperinsulinaemic Hypoglycaemia ◽  
Whole Exome ◽  
Glucokinase Mutation

Objective In adults with hyperinsulinaemic hypoglycaemia (HH), in particular those with insulinoma, the optimal diagnostic and management strategies remain uncertain. Here, we sought to characterise the biochemical and radiological assessment, and clinical management of adults with HH at a tertiary centre over a thirteen-year period. Design Clinical, biochemical, radiological and histological data were reviewed from all confirmed cases of adult-onset hyperinsulinaemic hypoglycaemia at our centre between 2003 and 2016. In a subset of patients with stage I insulinoma, whole-exome sequencing of tumour DNA was performed. Results Twenty-nine patients were identified (27 insulinoma, including 6 subjects with metastatic disease; 1 pro-insulin/GLP-1 co-secreting tumour; 1 activating glucokinase mutation). In all cases, hypoglycaemia (glucose ≤2.2 mmol/L) was achieved within 48 h of a supervised fast. At fast termination, subjects with stage IV insulinoma had significantly higher insulin, C-peptide and pro-insulin compared to those with insulinoma staged I–IIIB. Preoperative localisation of insulinoma was most successfully achieved with EUS. In two patients with inoperable, metastatic insulinoma, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE rapidly restored euglycaemia and lowered fasting insulin. Finally, in a subset of stage I insulinoma, whole-exome sequencing of tumour DNA identified the pathogenic Ying Yang-1 (YY1) somatic mutation (c.C1115G/p.T372R) in one tumour, with all tumours exhibiting a low somatic mutation burden. Conclusion Our study highlights, in particular, the utility of the 48-h fast in the diagnosis of insulinoma, EUS for tumour localisation and the value of PRRT therapy in the treatment of metastatic disease.

scholarly journals Whole Exome Sequencing Identifies an Adult-Onset Case of Methylmalonic Aciduria and Homocystinuria Type C (cblC) with Non-Syndromic Bull’s Eye Maculopathy

2015 ◽  
Vol 36 (3) ◽  
pp. 270-275 ◽  
Author(s):  
Frederick T. Collison ◽  
Yajing (Angela) Xie ◽  
Tomasz Gambin ◽  
Shalini Jhangiani ◽  
Donna Muzny ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Methylmalonic Aciduria ◽  
Adult Onset ◽  
Whole Exome ◽  
Bull’S Eye Maculopathy ◽  
Type C ◽  
Bull's Eye

scholarly journals Should we Investigate Mitochondrial Disorders in Progressive Adult-onset Undetermined Ataxias?

2020 ◽  
Author(s):  
José Luiz Pedroso ◽  
Wladimir B Rezende Pinto ◽  
Orlando G Barsottini ◽  
Acary S B Oliveira
Keyword(s):  
Mitochondrial Dna ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Muscle Biopsy ◽  
Nuclear Dna ◽  
Late Onset ◽  
Mitochondrial Disorders ◽  
Adult Onset ◽  
Whole Exome ◽  
Merrf Syndrome

Abstract Background: Despite the broad development of next-generation sequencing approaches recently, such as whole-exome sequencing, diagnostic workup of adult-onset progressive cerebellar ataxias without remarkable family history and with negative genetic panel testing for SCAs remains a complex and expensive clinical challenge. Case presentation: In this article, we report a Brazilian man with adult-onset slowly progressive pure cerebellar ataxia, which developed neuropathy and hearing loss after fifteen years of ataxia onset, in which a primary mitochondrial DNA defect (MERRF syndrome - myoclonus epilepsy with ragged-red fibers) was confirmed through muscle biopsy evaluation and whole-exome sequencing. Conclusions: Mitochondrial disorders are a clinically and genetically complex and heterogenous group of metabolic diseases, resulting from pathogenic variants in the mitochondrial DNA or nuclear DNA. In our case, a correlation with histopathological changes identified on muscle biopsy helped to clarify the definitive diagnosis. Moreover, in neurodegenerative and neurogenetic disorders, some symptoms may be evinced later during disease course. We suggest that late-onset and adult pure undetermined ataxias should be considered and investigated for mitochondrial disorders, particularly MERRF syndrome and other primary mitochondrial DNA defects, together with other more commonly known nuclear genes.

scholarly journals A novel somatic mutation of SIN3A detected in breast cancer by whole-exome sequencing enhances cell proliferation through ERα expression

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Kenji Watanabe ◽  
Shigeru Yamamoto ◽  
Syuiti Sakaguti ◽  
Keishiro Isayama ◽  
Masaaki Oka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Somatic Mutation ◽  
Whole Exome

Whole-exome sequencing in tumor samples from sequenom-wild-type, ALK negative stage IV lung adenocarcinoma (ADC) patients (p).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8070-8070
Author(s):  
Enriqueta Felip ◽  
Ginevra Caratu ◽  
Daniel Silberschmidt ◽  
Pablo Martinez ◽  
Alex Martinez Marti ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Transmembrane Domain ◽  
Lung Tumor ◽  
Stage Iv ◽  
Genetic Alterations ◽  
Wild Type ◽  
Kras Mutations ◽  
Tissue Samples ◽  
Whole Exome

8070 Background: The majority of lung ADC tumors are characterized by specific genetic features with KRAS mutations (mut) seen in 20-30%, EGFR mut in 15%, EML4-ALK translocations in 5%, and ERBB2 mut in 2%, among others. Some of these genetic alterations are already being used for selecting targeted therapies. However, identification of additional genomic alterations is required. Methods: In the present ongoing study we perform whole-exome sequencing in paraffin-embedded tumor samples from OncoCarta v1.0 panel wild-type (no mut in hotspots of KRAS, EGFR, ERBB2, AKT1, BRAF, PIK3CA genes) and ALK negative (by FISH) stage IV ADC lung cancer p, and in their matched normal tissue samples. Results: To date, a total of 7 tumors and matched normal tissues have been successfully analyzed. We have detected mut in previously identified ADC genes, such as ERBB2, CTNNB1, TP53, SMAD4 or APC. Interestingly, mut were found in genes belonging to the proposed new cancer hallmark ‘epigenetic and RNA regulation’, such as BRD3, EPC1, PHF1 in almost every p included in our study. Regarding alterations that could be considered relevant for lung tumor pathogenesis/growth or as potential targets for treatment therapies, we were able to identify candidates in 4 of the 7 p. In one p, a case of a transmembrane domain ERBB2mut in exon 20 (p.E770delinsEAYVM) not previously detected by the OncoCarta v1.0 panel (that interrogates L755P, G776S/L/V/C, A775_G776insYVMA, P780_Y781insGSP, S779_P780insVGS mut) was found. In another p, three somatic mut in the BRCA1/2 genes were detected. Additionally, one p had an ALK point mut (p.P336K), for which no functional information is available, together with an APC mutation. In the remaining p, a non-hotspot mutation (although previously detected in a colorectal tumor) was found in CTNNB1. Conclusions: In this limited experience of whole-exome sequencing of a subgroup of stage IV lung ADC p, potentially targetable alterations not formerly detected by other techniques were found. We believe that genomic approaches to detecting alterations may be useful in clinical practice and will hopefully provide assistance in making treatment decisions.

scholarly journals DNN-Boost: Somatic mutation identification of tumor-only whole-exome sequencing data using deep neural network and XGBoost

2021 ◽  
Author(s):  
Firda Aminy Maruf ◽  
Rian Pratama ◽  
Giltae Song
Keyword(s):  
Neural Network ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Somatic Mutation ◽  
Deep Neural Network ◽  
Somatic Mutations ◽  
Sequencing Data ◽  
Exome Sequencing Data ◽  
Whole Exome ◽  
Whole Exome Sequencing Data

Detection of somatic mutation in whole-exome sequencing data can help elucidate the mechanism of tumor progression. Most computational approaches require exome sequencing for both tumor and normal samples. However, it is more common to sequence exomes for tumor samples only without the paired normal samples. To include these types of data for extensive studies on the process of tumorigenesis, it is necessary to develop an approach for identifying somatic mutations using tumor exome sequencing data only. In this study, we designed a machine learning approach using Deep Neural Network (DNN) and XGBoost to identify somatic mutations in tumor-only exome sequencing data and we integrated this into a pipeline called DNN-Boost. The XGBoost algorithm is used to extract the features from the results of variant callers and these features are then fed into the DNN model as input. The XGBoost algorithm resolves issues of missing values and overfitting. We evaluated our proposed model and compared its performance with other existing benchmark methods. We noted that the DNN-Boost classification model outperformed the benchmark method in classifying somatic mutations from paired tumor-normal exome data and tumor-only exome data.

scholarly journals Whole-exome sequencing of polycythemia vera revealed novel driver genes and somatic mutation shared by T cells and granulocytes

Leukemia ◽  
2014 ◽  
Vol 28 (4) ◽  
pp. 935-938 ◽  
Author(s):  
L Wang ◽  
S I Swierczek ◽  
J Drummond ◽  
K Hickman ◽  
SJ Kim ◽  
...  
Keyword(s):  
T Cells ◽  
Polycythemia Vera ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Somatic Mutation ◽  
Driver Genes ◽  
Whole Exome
Sign in / Sign up

Export Citation Format

Share Document