Detection of Molecular Alterations in Medullary Thyroid Carcinoma Using Next-Generation Sequencing: an Institutional Experience

2016 ◽  
Vol 27 (4) ◽  
pp. 359-362 ◽  
Author(s):  
Shuanzeng Wei ◽  
Virginia A. LiVolsi ◽  
Kathleen T. Montone ◽  
Jennifer J. D. Morrissette ◽  
Zubair W. Baloch
Keyword(s):  
Next Generation Sequencing ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Next Generation ◽  
Medullary Thyroid ◽  
Molecular Alterations ◽  
Institutional Experience ◽  
Generation Sequencing

scholarly journals Next-generation panel sequencing identifies NF1 germline mutations in three patients with pheochromocytoma but no clinical diagnosis of neurofibromatosis type 1

2018 ◽  
Vol 178 (2) ◽  
pp. K1-K9 ◽  
Author(s):  
Laura Gieldon ◽  
Jimmy Rusdian Masjkur ◽  
Susan Richter ◽  
Roland Därr ◽  
Marcos Lahera ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Clinical Diagnosis ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Germline Mutations ◽  
Next Generation ◽  
Medullary Thyroid

Objective Our objective was to improve molecular diagnostics in patients with hereditary pheochromocytoma and paraganglioma (PPGL) by using next-generation sequencing (NGS) multi-gene panel analysis. Derived from this study, we here present three cases that were diagnosed with NF1 germline mutations but did not have a prior clinical diagnosis of neurofibromatosis type 1 (NF1). Design We performed genetic analysis of known tumor predisposition genes, including NF1, using a multi-gene NGS enrichment-based panel applied to a total of 1029 PPGL patients. We did not exclude genes known to cause clinically defined syndromes such as NF1 based on missing phenotypic expression as is commonly practiced. Methods Genetic analysis was performed using NGS (TruSight Cancer Panel/customized panel by Illumina) for analyzing patients’ blood and tumor samples. Validation was carried out by Sanger sequencing. Results Within our cohort, three patients, who were identified to carry pathogenic NF1 germline mutations, attracted attention, since none of the patients had a clinical suspicion of NF1 and one of them was initially suspected to have MEN2A syndrome due to co-occurrence of a medullary thyroid carcinoma. In these cases, one splice site, one stop and one frameshift mutation in NF1 were identified. Conclusions Since phenotypical presentation of NF1 is highly variable, we suggest analysis of the NF1 gene also in PPGL patients who do not meet diagnostic NF1 criteria. Co-occurrence of medullary thyroid carcinoma and PPGL was found to be a clinical decoy in NF1 diagnostics. These observations underline the value of multi-gene panel NGS for PPGL patients.

The long tail of molecular alterations in non-small cell lung cancer: a single-institution experience of next-generation sequencing in clinical molecular diagnostics

2018 ◽  
Vol 71 (9) ◽  
pp. 767-773 ◽  
Author(s):  
Caterina Fumagalli ◽  
Davide Vacirca ◽  
Alessandra Rappa ◽  
Antonio Passaro ◽  
Juliana Guarize ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Diagnostics ◽  
Small Cell ◽  
Next Generation ◽  
Small Cell Lung ◽  
Single Institution ◽  
Lung Cancers ◽  
Targeted Next Generation Sequencing ◽  
Molecular Alterations ◽  
Generation Sequencing

BackgroundMolecular profiling of advanced non-small cell lung cancers (NSCLC) is essential to identify patients who may benefit from targeted treatments. In the last years, the number of potentially actionable molecular alterations has rapidly increased. Next-generation sequencing allows for the analysis of multiple genes simultaneously.AimsTo evaluate the feasibility and the throughput of next-generation sequencing in clinical molecular diagnostics of advanced NSCLC.MethodsA single-institution cohort of 535 non-squamous NSCLC was profiled using a next-generation sequencing panel targeting 22 actionable and cancer-related genes.Results441 non-squamous NSCLC (82.4%) harboured at least one gene alteration, including 340 cases (63.6%) with clinically relevant molecular aberrations. Mutations have been detected in all but one gene (FGFR1) of the panel. Recurrent alterations were observed in KRAS, TP53, EGFR, STK11 and MET genes, whereas the remaining genes were mutated in <5% of the cases. Concurrent mutations were detected in 183 tumours (34.2%), mostly impairing KRAS or EGFR in association with TP53 alterations.ConclusionsThe study highlights the feasibility of targeted next-generation sequencing in clinical setting. The majority of NSCLC harboured mutations in clinically relevant genes, thus identifying patients who might benefit from different targeted therapies.

Searching for Non-RET Molecular Alterations in Medullary Thyroid Carcinoma: Expression Analysis by mRNA Differential Display

2005 ◽  
Vol 29 (4) ◽  
pp. 472-482 ◽  
Author(s):  
Thomas J. Musholt ◽  
Julia Hanack ◽  
Christoph Brehm ◽  
Reinhard von Wasielewski ◽  
Petra B. Musholt
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Expression Analysis ◽  
Differential Display ◽  
Mrna Differential Display ◽  
Medullary Thyroid ◽  
Molecular Alterations

Enabling Precision Oncology Through Precision Diagnostics

2020 ◽  
Vol 15 (1) ◽  
pp. 97-121 ◽  
Author(s):  
Noah A. Brown ◽  
Kojo S.J. Elenitoba-Johnson
Keyword(s):  
Next Generation Sequencing ◽  
Cancer Patients ◽  
Cancer Genomics ◽  
Cost Effective ◽  
Routine Clinical Practice ◽  
Precision Oncology ◽  
Next Generation ◽  
Sequencing Data ◽  
Molecular Alterations ◽  
Generation Sequencing

Genomic testing enables clinical management to be tailored to individual cancer patients based on the molecular alterations present within cancer cells. Genomic sequencing results can be applied to detect and classify cancer, predict prognosis, and target therapies. Next-generation sequencing has revolutionized the field of cancer genomics by enabling rapid and cost-effective sequencing of large portions of the genome. With this technology, precision oncology is quickly becoming a realized paradigm for managing the treatment of cancer patients. However, many challenges must be overcome to efficiently implement the transition of next-generation sequencing from research applications to routine clinical practice, including using specimens commonly available in the clinical setting; determining how to process, store, and manage large amounts of sequencing data; determining how to interpret and prioritize molecular findings; and coordinating health professionals from multiple disciplines.

scholarly journals Molecular profiling of congenital glioblastoma using a next-generation sequencing panel

2021 ◽  
Author(s):  
Débora Cabral de Carvalho Corrêa ◽  
Francine Tesser-Gamba ◽  
Nasjla da Silva ◽  
Andrea Capellano ◽  
Maria Teresa Alves ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Variants ◽  
Next Generation ◽  
Congenital Brain Tumor ◽  
Molecular Alterations ◽  
Pathogenic Variants ◽  
Pediatric Neoplasms ◽  
Tumor Entity ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Background Congenital GBM (cGBM), presenting prenatally or within the first months of life, is among the rarest type of congenital brain tumor, with approximately 120 cases reported. Due to its infrequent occurrence, few studies have focused on the molecular and genetic aspects of this tumor, and the mutational events involved in the pathogenesis and progression of cGBM still remains poorly understood. This study aimed to investigate molecular alterations, with a potential prognostic marker and therapeutic target in cGBM using the next-generation sequencing (NGS) strategy. Methods We selected seven tumor samples from patients diagnosed with cGBM and treated at Pediatric Oncology Institute-GRAACC/UNIFESP. NGS was performed to identify somatic genetic variants in tumor samples using the Oncomine Childhood Cancer Research Assay panel, from ThermoFisher Scientific, designed specifically for pediatric neoplasms. Results Of all seven patients analyzed, three patients exhibited tumors with genetic variants, which include two pathogenic variants in NF1 and SUZ12 genes that have not been reported in cGBM yet, an increase in the number of copies of ALK gene, and two gene fusions, PPP1CB-ALK and TPM3-NTRK1. Also, none of the cases showed variants in H3F3A, TP53 and ATRX genes, alterations which are frequently seen in pediatric and adolescent GBM. Conclusions Our results suggest that cGBM may comprise a unique tumor entity and alterations in ALK and NTRK genes provide a potential target for therapy. Therefore, identification of genetic variants in cGBM is highly relevant in order to define prognosis and therapeutic strategies.

Next-generation sequencing of esophageal carcinosarcoma to reveal high frequency of actionable PIK3CA gene mutations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15503-e15503
Author(s):  
Hongyang Lu ◽  
Shifeng Yang ◽  
Zhiming Jiang ◽  
Fajun Xie ◽  
Jing Qin ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Gene Mutations ◽  
Single Copy ◽  
Next Generation ◽  
Old Patients ◽  
Molecular Alterations ◽  
Anaplastic Lymphoma ◽  
Esophageal Carcinosarcoma ◽  
Clinical Characteristic ◽  
Generation Sequencing

e15503 Background: Esophageal carcinosarcoma (ESC) is a rare malignant esophageal neoplasm consisting of both carcinomatous and sarcomatous components. Drive genes mutations may potentially serve as novel biomarkers to targeted therapy in ESC, and they also may explain the mechanisms of the unique dual-differentiation pattern. Actionable gene alterations with any significant frequency in ESC were unknown due to specimen numbers and limited studies. A comprehensive study of clinical characteristic and molecular alterations in ESC is needed to better understand biology and guide therapy. Methods: Fifteen cases of ESCs which received surgical resection were retrospectively collected from the Zhejiang Cancer Hospital in China between 2009 and 2016, next generation sequencing was performed to identify genotypic changes, and clinical characteristic of these patients was also collected and analyzed. Results: ESC patients are easily occurred in male, heavy smokers, and old patients. The mainly gross types were medullary and fungating type. Mutation of phosphatase and tensin homologue ( PTEN), MAP2K1(MEK1), anaplastic lymphoma kinase ( ALK), RET, and NF1 were detected in one patient respectively. Mutation of ERBB2(HER2), MET and single copy loss of Rb1 were detected in two patients respectively. Mutation of ROS1 and phosphoinositide-3-kinase catalytic alpha ( PIK3CA) were detected in three patients respectively. Conclusions:PIK/AKT pathway may be important in pathogenesis of ESCs, and it may be an ideal therapeutic target.

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