Unexpected diagnosis of multiple sclerosing pneumocytomas in a patient with chondrosarcoma of the hand

2021 ◽  
Vol 14 (1) ◽  
pp. e238375
Author(s):  
Sven L Van Laer ◽  
Annelore Vandendriessche ◽  
Johan Somville ◽  
Paul E Van Schil
Keyword(s):  
Lung Metastases ◽  
Gene Mutations ◽  
Pulmonary Nodules ◽  
Immunohistochemical Analysis ◽  
Idh1 Mutation ◽  
Caucasian Woman ◽  
Diagnostic Challenge ◽  
Next Generation Sequencing Ngs ◽  
Gene Mutation Analysis ◽  
Generation Sequencing

Sclerosing pneumocytomas are rare, benign pulmonary neoplasms that predominantly affect Asian female patients in the age category of 40–70 years, mostly non-smokers. We report on a 72-year-old Caucasian woman with chondrosarcoma of the hand who developed multiple bilateral progressive lung nodules suspicious of lung metastases. Staged lung resections were performed, and pathological diagnosis was confirmed by immunohistochemical analysis of the resected specimens. Next-generation sequencing (NGS) was used to detect gene mutations. Immunohistochemistry demonstrated sclerosing pneumocytomas, and NGS showed an IDH1 mutation. Eventually, the patient developed lung metastases for which rethoracotomy was performed. The differentiation of sclerosing pneumocytoma from lung cancer is a diagnostic challenge, and sclerosing pneumocytoma should be considered in the differential diagnosis of pulmonary nodules. Gene mutation analysis does not always show classical and common mutations, which should be kept in mind when interpreting its results.

scholarly journals Jervell and Lange-Nielsen Syndrome due to a Novel Compound Heterozygous KCNQ1 Mutation in a Chinese Family

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yue Qiu ◽  
Sen Chen ◽  
Xia Wu ◽  
Wen-Juan Zhang ◽  
Wen Xie ◽  
...  
Keyword(s):  
Deaf Child ◽  
Gene Mutations ◽  
Deaf Children ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Qtc Interval ◽  
Cardiac Events ◽  
Life Threatening ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Jervell and Lange-Nielsen syndrome (JLNS) is a rare but severe autosomal recessive disease characterized by profound congenital deafness and a prolonged QTc interval (greater than 500 milliseconds) in the ECG waveforms. The prevalence of JLNS is about 1/1000000 to 1/200000 around the world. However, exceed 25% of JLNS patients suffered sudden cardiac death with kinds of triggers containing anesthesia. Approximately 90% of JLNS cases are caused by KCNQ1 gene mutations. Here, using next-generation sequencing (NGS), we identified a compound heterozygosity for two mutations c.1741A>T (novel) and c.477+5G>A (known) in KCNQ1 gene as the possible pathogenic cause of JLNS, which suggested a high risk of cardiac events in a deaf child. The hearing of this patient improved significantly with the help of cochlear implantation (CI). But life-threatening arrhythmias occurred with a trigger of anesthesia after the end of the CI surgery. Our findings extend the KCNQ1 gene mutation spectrum and contribute to the management of deaf children diagnosed with JLNS for otolaryngologists (especially cochlear implant teams).

scholarly journals Targeted Next Generation Sequencing (NGS) to Diagnose Hereditary Hemolytic Anemias

2020 ◽  
Author(s):  
Rishab Bharadwaj ◽  
Thulasi Raman ◽  
Ravikumar Thangadorai ◽  
Deenadayalan Munirathnam
Keyword(s):  
Next Generation Sequencing ◽  
Gene Sequencing ◽  
Accurate Diagnosis ◽  
Next Generation ◽  
Diagnostic Challenge ◽  
Targeted Next Generation Sequencing ◽  
Appropriate Treatment ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Hereditary hemolytic anemias present a unique diagnostic challenge due to their wide phenotypic and genotypic spectrum. Accurate diagnosis is essential to ensure appropriate treatment. We report two cases, which presented as hemolytic anemias, but initial workup was inconclusive and they were finally diagnosed with the help of Next Generation Sequencing (Dehydrated Hereditary Stomatocytosis and Kӧln Hemoglobinopathy). The introduction of gene sequencing to aid diagnosis of these disorders is a revolutionary step forward and should be incorporated earlier in the workup of such patients.

scholarly journals Methylmalonic Acidemia with Novel MUT Gene Mutations

2017 ◽  
Vol 2017 ◽  
pp. 1-2
Author(s):  
Inusha Panigrahi ◽  
Savita Bhunwal ◽  
Harish Varma ◽  
Simranjeet Singh
Keyword(s):  
Sanger Sequencing ◽  
Gene Mutations ◽  
Methylmalonic Acidemia ◽  
Feeding Problems ◽  
Novel Variants ◽  
Mut Gene ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Poor Weight Gain

A 5-year-old boy presented with recurrent episodes of fever, feeding problems, lethargy, from the age of 11 months, and poor weight gain. He was admitted and evaluated for metabolic causes and diagnosed as having methylmalonic acidemia (MMA). He was treated with vit B12 and carnitine supplements and has been on follow-up for the last 3 years. Mutation analysis by next generation sequencing (NGS), supplemented with Sanger sequencing, revealed two novel variants in the MUT gene responsible for MMA in exon 5 and exon 3, respectively. Recently he developed dystonic movements including orofacial dyskinesia. With advent of NGS, judicious use of NGS with Sanger sequencing can help identify causative possibly pathogenic mutations.

scholarly journals The Potential Role of Aldosterone-Producing Cell Clusters in Adrenal Disease

2020 ◽  
Vol 52 (06) ◽  
pp. 427-434
Author(s):  
Jung Soo Lim ◽  
William E. Rainey
Keyword(s):  
Gene Mutations ◽  
Normal Subjects ◽  
Secondary Hypertension ◽  
Cell Clusters ◽  
Somatic Gene ◽  
Aldosterone Production ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Made In

AbstractPrimary aldosteronism (PA) is the most common cause of secondary hypertension. The hallmark of PA is adrenal production of aldosterone under suppressed renin conditions. PA subtypes include adrenal unilateral and bilateral hyperaldosteronism. Considerable progress has been made in defining the role for somatic gene mutations in aldosterone-producing adenomas (APA) as the primary cause of unilateral PA. This includes the use of next-generation sequencing (NGS) to define recurrent somatic mutations in APA that disrupt calcium signaling, increase aldosterone synthase (CYP11B2) expression, and aldosterone production. The use of CYP11B2 immunohistochemistry on adrenal glands from normal subjects, patients with unilateral and bilateral PA has allowed the identification of CYP11B2-positive cell foci, termed aldosterone-producing cell clusters (APCC). APCC lie beneath the adrenal capsule and like APA, many APCC harbor somatic gene mutations known to increase aldosterone production. These findings suggest that APCC may play a role in pathologic progression of PA. Herein, we provide an update on recent research directed at characterizing APCC and also discuss the unanswered questions related to the role of APCC in PA.

scholarly journals NGS-Based Analysis of Atypical Deep Penetrating Nevi

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3066
Author(s):  
Antonella Manca ◽  
Maria Cristina Sini ◽  
Anna Maria Cesinaro ◽  
Francesca Portelli ◽  
Carmelo Urso ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Metastatic Potential ◽  
Idh1 Mutation ◽  
Specific Gene ◽  
Nodal Disease ◽  
Architectural Features ◽  
Frequent Mutations ◽  
Map Kinase Pathway ◽  
Kinase Pathway ◽  
Generation Sequencing

Deep penetrating nevi (DPNs) are rare melanocytic neoplasms consisting of pigmented spindled or epithelioid melanocytes with a distinctive wedge-shaped configuration showing activation of the WNT pathway, with unusual cyto-architectural features. It is unclear whether they show a distinct genomic profile associated with a diverse metastatic potential. We describe herein a cohort of 21 atypical DPNs analyzed by next-generation sequencing using the Ion AmpliSeq™ Comprehensive Cancer Panel. We found that β-catenin exon 3 was mutated in 95% and MAP kinase pathway genes in 71% of the cases. Less frequent mutations were observed in HRAS (19%) and MAP2K1 (24%). Isocitrate dehydrogenases 1 (IDH1) mutations, including R132C, V178I, and S278L, were identified in 38% of cases and co-existed with BRAF/HRAS mutations. The only case with progressive nodal disease carried alterations in the β-catenin pathway and mutations in IDH1 and NRAS (codon 61). By a comprehensive mutation analysis, we found low genetic heterogeneity and a lack of significant associations between specific gene mutations and histopathological features, despite atypical features. Whether the acquisition of an NRAS or IDH1 mutation in an atypical DPN may represent a molecular evolution implying a pathway to melanoma progression should be confirmed in a larger series.

scholarly journals Novel RB1 and MET Gene Mutations in a Case with Bilateral Retinoblastoma Followed by Multiple Metastatic Osteosarcoma

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 28
Author(s):  
Attila Mokánszki ◽  
Yi-Che Chang Chien ◽  
János András Mótyán ◽  
Péter Juhász ◽  
Emese Sarolta Bádon ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Genetic Alterations ◽  
Causative Role ◽  
Rb1 Gene ◽  
Tissue Samples ◽  
Metastatic Osteosarcoma ◽  
Bilateral Retinoblastoma ◽  
Chondroblastic Osteosarcoma ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Retinoblastoma (Rb) is a malignant tumor of the developing retina that affects children before the age of five years in association with inherited or early germline mutations of the RB1 gene. The genetic predisposition is also a driver for other primary malignancies, which have become the leading cause of death in retinoblastoma survivors. Other malignancies can occur as a consequence of radiotherapy. We describe a patient with retinoblastoma in which we detected a novel RB1 c.2548C > T, p.(Gln850Ter) and a synchronous MET c.3029C > T, p.(Thr1010Ile) mutation as well. After presenting with bilateral retinoblastoma, the patient developed at least four different manifestations of two independent osteosarcomas. Our goal was to identify all germline and somatic genetic alterations in available tissue samples from different time periods and to reconstruct their clonal relations using next generation sequencing (NGS). We also used structural and functional prediction of the mutant RB and MET proteins to find interactions between the defected proteins with potential causative role in the development of this unique form of retinoblastoma. Both histopathology and NGS findings supported the independent nature of a chondroblastic osteosarcoma of the irradiated facial bone followed by an osteoblastic sarcoma of the leg (tibia).

scholarly journals Liquid Biopsy Using Ascites and Pleural Effusion Supernatant for Genomic Profiling in Gastrointestinal and Lung Cancers

2021 ◽  
Author(s):  
Hui-Ta Wu ◽  
Hao-Nan Ji ◽  
Wen-Hui Yang ◽  
Min Zhang ◽  
Yi-Fang Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Pleural Effusion ◽  
Mutation Rate ◽  
Gene Mutations ◽  
Specific Gene ◽  
Genomic Profiling ◽  
Next Generation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Background: Precision medicine highlights the importance of incorporating molecular genetic testing into standard clinical care. Next-generation sequencing (NGS) can detect cancer-specific gene mutations, and molecular targeted drugs can be designed to be effective for one or more specific gene mutations. For patients with special site metastasis, it is particularly important to use appropriate samples for genetic profiling test.Methods: Tissues, plasma, ascites (ASC) supernatants, pleural effusion (PE) samples from gastrointestinal (GI) patients with peritoneal metastasis and lung cancer patients with pleural metastasis were collected for comprehensive genomic profiling. The sample were performed on next-generation sequencing (NGS) using 59 or 1021 cancer-relevant genes panel. Results: The study enrolled 156 tissues, 188 plasma, 45 ascites supernatants, and 1 pleural effusion in 304 GI group and 446 pleural effusion supernatants, 122 tissues, 389 plasma, 45 pleural effusion sediments in 407 lung cancer group. The MSAF were significantly higher in ASC and PE supernatant than plasma ctDNA (50.18% ± 32.03% vs 12.31% ± 19.90%, p < 0.0001 and 33.74% ± 28.34% vs 6.28% ± 12.17%, p < 0.0001, respectively). ASC supernatant had a higher actionable mutation rate than plasma. ASC supernatant accounts for more actionable alterations than plasma ctDNA in 26 paired samples. PE supernatant had higher total actionable mutation rate than plasma (80.3% vs 48.4%, p < 0.05). PE supernatant had a higher frequency of uncommon variations than plasma no matter had distant organ metastasis. Conclusion: ASC and PE supernatants could be better alternatives when tumor tissues are not available in the real world, especially in patients who have only peritoneal or pleural metastases.

scholarly journals Less frequently mutated genes in colorectal cancer: evidences from next-generation sequencing of 653 routine cases

2016 ◽  
Vol 69 (9) ◽  
pp. 767-771 ◽  
Author(s):  
Umberto Malapelle ◽  
Pasquale Pisapia ◽  
Roberta Sgariglia ◽  
Elena Vigliar ◽  
Maria Biglietto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Somatic Mutations ◽  
Gene Mutations ◽  
Next Generation ◽  
Genomic Landscape ◽  
Next Generation Sequencing Ngs ◽  
Pcr Targeting ◽  
Diagnostic Setting ◽  
Generation Sequencing

AimsThe incidence of RAS/RAF/PI3KA and TP53 gene mutations in colorectal cancer (CRC) is well established. Less information, however, is available on other components of the CRC genomic landscape, which are potential CRC prognostic/predictive markers.MethodsFollowing a previous validation study, ion-semiconductor next-generation sequencing (NGS) was employed to process 653 routine CRC samples by a multiplex PCR targeting 91 hotspot regions in 22 CRC significant genes.ResultsA total of 796 somatic mutations in 499 (76.4%) tumours were detected. Besides RAS/RAF/PI3KA and TP53, other 12 genes showed at least one mutation including FBXW7 (6%), PTEN (2.8%), SMAD4 (2.1%), EGFR (1.2%), CTNNB1 (1.1%), AKT1 (0.9%), STK11 (0.8%), ERBB2 (0.6%), ERBB4 (0.6%), ALK (0.2%), MAP2K1 (0.2%) and NOTCH1 (0.2%).ConclusionsIn a routine diagnostic setting, NGS had the potential to generate robust and comprehensive genetic information also including less frequently mutated genes potentially relevant for prognostic assessments or for actionable treatments.

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