scholarly journals Targeted next-generation sequencing of CIC-DUX4 soft tissue sarcomas demonstrates low mutational burden and recurrent chromosome 1p loss

2016 ◽  
Vol 58 ◽  
pp. 161-170 ◽  
Author(s):  
Lorena Lazo de la Vega ◽  
Daniel H. Hovelson ◽  
Andi K. Cani ◽  
Chia-Jen Liu ◽  
Jonathan B. McHugh ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Chromosome 1P ◽  
Mutational Burden ◽  
Generation Sequencing

scholarly journals Targeted Next-Generation Sequencing of Cancer-Related Genes in a Norwegian Patient Cohort With Head and Neck Squamous Cell Carcinoma Reveals Novel Actionable Mutations and Correlations With Pathological Parameters

2021 ◽  
Vol 11 ◽  
Author(s):  
Harsh N. Dongre ◽  
Hilde Haave ◽  
Siren Fromreide ◽  
Fredrik A. Erland ◽  
Svein Erik Emblem Moe ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Head And Neck ◽  
Squamous Cell ◽  
Ffpe Tissue ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Mutational Burden ◽  
Custom Made ◽  
Targeted Ngs ◽  
Generation Sequencing

BackgroundTargeted next-generation sequencing (NGS) is increasingly applied in clinical oncology to advance personalized treatment. Despite success in many other tumour types, use of targeted NGS panels for assisting diagnosis and treatment of head and neck squamous cell carcinomas (HNSCC) is still limited.AimThe focus of this study was to establish a robust NGS panel targeting most frequent cancer mutations in long-term preserved formalin-fixed paraffin-embedded (FFPE) tissue samples of HNSCC from routine diagnostics.Materials and MethodsTumour DNA obtained from archival FFPE tissue blocks of HNSCC patients treated at Haukeland University Hospital between 2003-2016 (n=111) was subjected to mutational analysis using a custom made AmpliSeq Library PLUS panel targeting 31 genes (Illumina). Associations between mutational burden and clinical and pathological parameters were investigated. Mutation and corresponding clinicopathological data from HNSCC were extracted for selected genes from the Cancer Genome Atlas (TCGA) and used for Chi-square and Kaplan-Meier analysis.ResultsThe threshold for sufficient number of reads was attained in 104 (93.7%) cases. Although the specific number of PCR amplified reads detected decreased, the number of NGS-annotated mutations did not significantly change with increased tissue preservation time. In HPV-negative carcinomas, mutations were detected mainly in TP53 (73.3%), FAT1 (26.7%) and FLG (16.7%) whereas in HPV-positive, the common mutations were in FLG (24.3%) FAT1 (17%) and FGFR3 (14.6%) genes. Other less common pathogenic mutations, including well reported SNPs were reproducibly identified. Presence of at least one cancer-specific mutations was found to be positively associated with an extensive desmoplastic stroma (p=0.019), and an aggressive type of invasive front (p=0.035), and negatively associated with the degree of differentiation (p=0.041). Analysis of TCGA data corroborated the association between cancer-specific mutations and tumour differentiation and survival analysis showed that tumours with at least one mutation had shorter disease-free and overall survival (p=0.005).ConclusionsA custom made targeted NGS panel could reliably detect several specific mutations in archival samples of HNSCCs preserved up to 17 years. Using this method novel associations between mutational burden and clinical and pathological parameters were detected and actionable mutations in HPV-positive HNSCC were discovered.

Molecular profiling of soft tissue sarcomas using next-generation sequencing: a pilot study toward precision therapeutics

2014 ◽  
Vol 45 (8) ◽  
pp. 1563-1571 ◽  
Author(s):  
George Jour ◽  
John D. Scarborough ◽  
Robin L. Jones ◽  
Elizabeth Loggers ◽  
Seth M. Pollack ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Pilot Study ◽  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Molecular Profiling ◽  
Next Generation ◽  
Generation Sequencing ◽  
Precision Therapeutics

Clinical benefit of next generation sequencing in soft tissue and bone sarcoma: Rush University Medical Center’s experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e22552-e22552
Author(s):  
Mia C. Weiss ◽  
Alan Blank ◽  
Steven Gitelis ◽  
Mary J. Fidler ◽  
Marta Batus
Keyword(s):  
Overall Survival ◽  
Next Generation Sequencing ◽  
Soft Tissue ◽  
Clinical Decision Making ◽  
Soft Tissue Sarcomas ◽  
Bone Sarcoma ◽  
Next Generation ◽  
Undifferentiated Sarcoma ◽  
The Impact ◽  
Generation Sequencing

e22552 Background: The overall survival for metastatic sarcoma has remained at only 18-20%. In the era of next generation sequencing (NGS), much research is ongoing on identifying optimal treatments. The MULTISARC trial aims to determine if NGS can lead to improved overall survival by randomizing patients with metastatic STS to receive NGS (followed by possible NGS-guided therapy) or not. We present our center’s experience with NGS in sarcomas patients. Methods: Patients with soft tissue and bone sarcomas at Rush that had the Foundation Medicine assay sent on tumor samples between August 2017 and August 2018 were analyzed retrospectively. The impact of NGS on clinical decision making was determined based on patients being prescribed off-label FDA-approved therapy targeting identified mutation. Results: Thirty-four patients with bone/soft tissue sarcomas that had NGS sent on specimens were identified. Median age at diagnosis: 43 (18-78 years); 18 males, 16 females. Histologic subtypes: synovial sarcoma, myxofibrosarcoma, leiomyosarcoma, chondrosarcoma, sclerosing epitheloid fibrosarcoma, PEcoma, pleomorphic undifferentiated sarcoma, MPNST, liposarcoma- well and de-differentiated, angiosarcoma, osteosarcoma. 16/34 patients had targetable mutations with approved therapies in tumor types other than sarcoma. Four of these patients had therapy changed based on NGS results, 1 patient with metastatic chondrosarcoma (PTEN mutation, everolimus added), 1 patient with metastatic liposarcoma (CDK4 mutation, palbociclib added), 1 patient with metastatic osteosarcoma (CCD1/CDK4 and a PDGFRA mutation for which palbociclib followed by imatinib was added), and 1 patient with metastatic pleomorphic undifferentiated sarcoma (CDK4 mutation, palbociclib added). Targetable mutations for which clinical trials are available were identified in 25/34 (73%) of the cases. Conclusions: NGS was readily able to identify actionable mutations in close to 50% of patients with clinical trial opportunities in close to 75%. Four patients had therapy changed as a result of NGS testing. Although our study size is small, our data show potential for the use of genomic profiling to identify actionable targets, tailor therapy, and hopefully improve outcomes. [Table: see text]

scholarly journals Qualification of tumour mutational burden by targeted next‐generation sequencing as a biomarker in hepatocellular carcinoma

2020 ◽  
Vol 41 (1) ◽  
pp. 192-203 ◽  
Author(s):  
Ching Ngar Wong ◽  
Petros Fessas ◽  
Kathy Dominy ◽  
Francesco A. Mauri ◽  
Takahiro Kaneko ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Mutational Burden ◽  
Generation Sequencing

Larotrectinib followed by selitrectinib in a novel DCTN1–NTRK1 fusion undifferentiated pleomorphic sarcoma

2020 ◽  
pp. 107815522093884
Author(s):  
Xue Na Goh ◽  
Michaela Su-Fern Seng ◽  
Amos Hong Pheng Loh ◽  
Achint Gupta ◽  
Kenneth Tou En Chang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Soft Tissue ◽  
Gene Fusion ◽  
Acquired Resistance ◽  
Resistance Mutation ◽  
Soft Tissue Sarcomas ◽  
Next Generation ◽  
Pleomorphic Sarcoma ◽  
Trk Inhibitors ◽  
Generation Sequencing

Introduction Neurotrophic receptor tyrosine kinase fusions cause overexpression or activation of kinase and are believed to confer oncogenic potential in some non-rhabdomyosarcoma soft tissue sarcomas. TRK inhibitors have recently been shown to induce responses in these tumours though current experience with these agents is still limited. Case report We report a case of an adolescent with treatment-refractory non-rhabdomyosarcoma soft tissue sarcomas, carrying a novel DCTN1–NTRK1 gene fusion whose progressive disease was treated with multi-kinase and TRK inhibitors. Management and outcome: Our patient was started on pan-TRK inhibitor larotrectinib, as his disease progressed after chemotherapy, radiation therapy and surgery, based on next-generation sequencing test showing DCTN1–NTRK1 gene fusion. He responded quickly to larotrectinib with the improvement of symptoms and reduction of masses. However, this response was short-lived due to the development of acquired solvent front resistance mutation. This patient did not respond to next-generation TRK inhibitor selitrectinib and eventually succumbed to his disease. Discussion The initial rapid and drastic response of our patient to larotrectinib was not sustained due to the development of acquired resistance. This case emphasizes the need for upfront and periodic next-generation sequencing testing to guide treatment of patients with refractory non-rhabdomyosarcoma soft tissue sarcomas.

Sign in / Sign up

Export Citation Format

Share Document