Genetic alterations in cfDNA of benign and malignant thyroid nodules based on amplicon-based next-generation sequencing

AbstractMixed phenotype acute leukemia (MPAL) is an uncommon disease characterized by currently only limited knowledge concerning biology, clinical presentation, and treatment outcome. We here describe a most unusual case of simultaneous occurrence of T-lymphoblastic lymphoma in cervical and mediastinal lymph nodes and acute myeloid leukemia in the bone marrow (BM) successfully treated with allogeneic stem cell transplantation (SCT). Although the blasts in both locations showed additional aberrant expression of other lineage markers (even B-cell markers), diagnostic criteria of MPAL were not fulfilled either in the LN or in the BM. We performed next generation sequencing (NGS) with the objective to look for common genetic aberrations in both tissues. Histology, immunohistochemistry, flow cytometry, AML-associated genetic alterations (FLT3, NPM1, KIT D816V, CEPBA), and clonal T-cell receptor β and γ gene rearrangements were performed according to routine diagnostic workflows. Next generation sequencing and Sanger sequencing were additionally performed in BM and LN. Somatic mutation in the EZH2 gene (p.(Arg684Cys)) was detected in the BM by NGS, and the same mutation was found in the LN. Since an identical genetic aberration (EZH2 mutation) was detected in both locations, a common progenitor with regional dependent differentiation may be involved.

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Targeted next-generation sequencing of colorectal cancer identified metastatic specific genetic alterations

BMC Proceedings ◽

10.1186/1753-6561-6-s6-p3 ◽

2012 ◽

Vol 6 (S6) ◽

Author(s):

A Rose Brannon ◽

Efsevia Vakiani ◽

Sasinya Scott ◽

Brooke Sylvester ◽

Krishan Kania ◽

...

Keyword(s):

Colorectal Cancer ◽

Next Generation Sequencing ◽

Genetic Alterations ◽

Next Generation ◽

Targeted Next Generation Sequencing ◽

Generation Sequencing

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Precision Oncology in Sarcomas: Divide and Conquer

JCO Precision Oncology ◽

10.1200/po.18.00247 ◽

2019 ◽

pp. 1-16 ◽

Cited By ~ 1

Author(s):

Roberto Carmagnani Pestana ◽

Roman Groisberg ◽

Jason Roszik ◽

Vivek Subbiah

Keyword(s):

Next Generation Sequencing ◽

Soft Tissue Sarcomas ◽

Genetic Alterations ◽

Divide And Conquer ◽

Precision Oncology ◽

Next Generation ◽

Mesenchymal Tumors ◽

Next Generation Sequencing Technology ◽

Molecular Abnormalities ◽

Generation Sequencing

Sarcomas are a heterogeneous group of rare malignancies that exhibit remarkable heterogeneity, with more than 50 subtypes recognized. Advances in next-generation sequencing technology have resulted in the discovery of genetic events in these mesenchymal tumors, which in addition to enhancing understanding of the biology, have opened up avenues for molecularly targeted therapy and immunotherapy. This review focuses on how incorporation of next-generation sequencing has affected drug development in sarcomas and strategies for optimizing precision oncology for these rare cancers. In a significant percentage of soft tissue sarcomas, which represent up to 40% of all sarcomas, specific driver molecular abnormalities have been identified. The challenge to evaluate these mutations across rare cancer subtypes requires the careful characterization of these genetic alterations to further define compelling drivers with therapeutic implications. Novel models of clinical trial design also are needed. This shift would entail sustained efforts by the sarcoma community to move from one-size-fits-all trials, in which all sarcomas are treated similarly, to divide-and-conquer subtype-specific strategies.

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The Application of Next-Generation Sequencing to Define Factors Related to Oral Cancer and Discover Novel Biomarkers

Life ◽

10.3390/life10100228 ◽

2020 ◽

Vol 10 (10) ◽

pp. 228

Author(s):

Soyeon Kim ◽

Joo Won Lee ◽

Young-Seok Park

Keyword(s):

Next Generation Sequencing ◽

Oral Cancer ◽

Genetic Alterations ◽

Eligibility Criterion ◽

Next Generation ◽

Novel Biomarkers ◽

Targeted Gene Therapy ◽

Next Generation Sequencing Ngs ◽

Potential Use ◽

Generation Sequencing

Despite the introduction of next-generation sequencing in the realm of DNA sequencing technology, it is not often used in the investigation of oral squamous cell carcinoma (OSCC). Oral cancer is one of the most frequently occurring malignancies in some parts of the world and has a high mortality rate. Patients with this malignancy are likely to have a poor prognosis and may suffer from severe facial deformity or mastication problems even after successful treatment. Therefore, a thorough understanding of this malignancy is essential to prevent and treat it. This review sought to highlight the contributions of next-generation sequencing (NGS) in unveiling the genetic alterations and differential expressions of miRNAs involved in OSCC progression. By applying an appropriate eligibility criterion, we selected relevant studies for review. Frequently identified mutations in genes such as TP53, NOTCH1, and PIK3CA are discussed. The findings of existing miRNAs (e.g., miR-21) as well as novel discoveries pertaining to OSCC are also covered. Lastly, we briefly mention the latest findings in targeted gene therapy and the potential use of miRNAs as biomarkers. Our goal is to encourage researchers to further adopt NGS in their studies and give an overview of the latest findings of OSCC treatment.

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Genetic Alterations Detected by Targeted Next-generation Sequencing and Their Clinical Implications in Neuroblastoma

Anticancer Research ◽

10.21873/anticanres.14733 ◽

2020 ◽

Vol 40 (12) ◽

pp. 7057-7065

Author(s):

KYUNG-NAM KOH ◽

JI-YOUNG LEE ◽

JINYEONG LIM ◽

JUHEE SHIN ◽

SUNG HAN KANG ◽

...

Keyword(s):

Next Generation Sequencing ◽

Genetic Alterations ◽

Clinical Implications ◽

Next Generation ◽

Targeted Next Generation Sequencing ◽

Generation Sequencing

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Next-Generation Sequencing Identifies Gene Mutations That Are Predictive of Malignancy in Residual Needle Rinses Collected From Fine-Needle Aspirations of Thyroid Nodules

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2017-0136-oa ◽

2017 ◽

Vol 142 (2) ◽

pp. 178-183 ◽

Cited By ~ 12

Author(s):

Maren Y. Fuller ◽

Dina Mody ◽

April Hull ◽

Kristi Pepper ◽

Heather Hendrickson ◽

...

Keyword(s):

Next Generation Sequencing ◽

Thyroid Nodules ◽

Gene Mutations ◽

Braf V600e ◽

Molecular Diagnostic ◽

Thyroid Malignancy ◽

Next Generation ◽

Fine Needle ◽

Thyroid Fna ◽

Generation Sequencing

Context.— Thyroid nodules have a prevalence of approximately 70% in adults. Fine-needle aspiration (FNA) is a minimally invasive, cost-effective, standard method to collect tissue from thyroid nodules for cytologic examination. However, approximately 15% of thyroid FNA specimens cannot be unambiguously diagnosed as benign or malignant. Objective.— To investigate whether clinically actionable data can be obtained using next-generation sequencing of residual needle rinse material. Design.— A total of 24 residual needle rinse specimens with malignant (n = 6), indeterminate (n = 9), or benign (n = 9) thyroid FNA diagnoses were analyzed in our clinical molecular diagnostics laboratory using next-generation sequencing assays designed to detect gene mutations and translocations that commonly occur in thyroid cancer. Results were correlated with surgical diagnoses and clinical outcomes. Results.— Interpretable data were generated from 23 of 24 residual needle rinse specimens. Consistent with its well-known role in thyroid malignancy, BRAF V600E mutations were detected in 4 malignant cases. An NRAS mutation was detected in 1 benign case. No mutations were detected from specimens with indeterminate diagnoses. Conclusions.— Our data demonstrate that residual thyroid FNA needle rinses are an adequate source of material for molecular diagnostic testing. Importantly, detection of a mutation implicated in thyroid malignancy was predictive of the final surgical diagnosis and clinical outcome. Our strategy to triage thyroid nodules with indeterminate cytology with molecular testing eliminates the need to perform additional FNA passes into dedicated media or to schedule additional invasive procedures. Further investigation with a larger sample size to confirm the clinical utility of our proposed strategy is underway.

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