Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with that of Orthogonal Methods for Detecting Targetable Genetic Alterations

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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Performance of next-generation sequencing for detection of clinically actionable genetic variants in cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.11099 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 11099-11099

Author(s):

Mohammed Omar Hussaini ◽

Ian S. Hagemann ◽

Teresa Mary Cox ◽

Christina Lockwood ◽

Karen Seibert ◽

...

Keyword(s):

Next Generation Sequencing ◽

Genetic Variants ◽

Simultaneous Detection ◽

Genetic Alterations ◽

Sequence Variants ◽

Tumor Type ◽

Cancer Genes ◽

Next Generation ◽

Therapeutic Implications ◽

Generation Sequencing

11099 Background: Next-generation sequencing (NGS) allows for simultaneous detection of numerous actionable somatic variants in cancer. We have implemented a clinical NGS panel to detect genetic alterations in 25 genes with established roles in cancer and report here the frequency of clinically actionable genetic variants in a variety of cancer types. Methods: NGS testing was performed in a CAP-certified, CLIA-licensed environment on DNA extracted from FFPE tissue in 209 cases spanning 41 histologic tumor types. DNA was enriched by hybrid capture and sequenced to >1,000x average coverage on Illumina sequencers with 2x101bp or 2x150bp reads. Variants were called using clinically validated parameters using the Genome Analysis Toolkit, Pindel, and the custom-written Clinical Genomicist Workstation. Results: Non-small cell lung cancer (45%), pancreatic cancer (10%), and colorectal cancer (8%) were the most common tumors sent for NGS analysis. An average of 3 (range 1- 16) non-synonymous, non-SNP sequence variants per case (SNVs and indels) were detected in the 130kb exonic target. Variants were most commonly seen in TP53, KRAS, and EGFR. 27% of cases (56/209) had one or more variants with therapeutic implications for the tumor type tested (e.g., EGFR mutation in NSCLC). 15% of cases (32/209) showed actionable variants not generally associated with the malignancy tested (e.g., detection of an activating KITvariant in thymic carcinoma). 10% of cases (21/209) had variants that were prognostically significant but not directly targetable. Some cases (9%) had variants that were prognostic/diagnostic and targetable. In 117 cases (56% of total), no therapeutically or prognostically significant variants were identified. Overall, in 92 cases (44%), NGS testing yielded information with therapeutic (majority), prognostic, or diagnostic ramifications. Conclusions: We found that 44% of unselected cancer cases have clinically relevant sequence variants in a set of 25 commonly mutated cancer genes. Our data suggest that clinical NGS testing may serve as an integral tool in realizing the potential of precision medicine in oncology.

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