دورية أكاديمية
Amplicon-Based NGS Panels for Actionable Cancer Target Identification in Follicular Cell-Derived Thyroid Neoplasia.
| العنوان: | Amplicon-Based NGS Panels for Actionable Cancer Target Identification in Follicular Cell-Derived Thyroid Neoplasia. |
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| المؤلفون: | Madsen MB; Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Kiss K; Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Cilius Nielsen F; Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Bennedbæk FN; Department of Endocrinology, Herlev University Hospital, Herlev, Denmark., Rossing M; Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. |
| المصدر: | Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2020 Mar 24; Vol. 11, pp. 146. Date of Electronic Publication: 2020 Mar 24 (Print Publication: 2020). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101555782 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2392 (Print) Linking ISSN: 16642392 NLM ISO Abbreviation: Front Endocrinol (Lausanne) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Mutation*, Adenocarcinoma, Follicular/*diagnosis , Biomarkers, Tumor/*genetics , DNA, Neoplasm/*analysis , High-Throughput Nucleotide Sequencing/*methods , Thyroid Neoplasms/*diagnosis, Adenocarcinoma, Follicular/genetics ; DNA, Neoplasm/genetics ; Humans ; Paraffin Embedding ; Thyroid Neoplasms/genetics ; Tissue Fixation |
| مستخلص: | Follicular cell-derived thyroid cancers are heterogenous and morphological classification is a complex and highly specialized task. Hence, identification of somatic alterations could provide insights to tumor biology and serve as an add-on diagnostic tool. Furthermore, results from these add-on tools could point in the direction of a more personalized treatment strategy. In the present study we set out to identify and validate the somatic mutation profile in a sample-set of follicular cell-derived thyroid neoplasia. One-hundred-and-one archived formalin fixed paraffin embedded (FFPE) tissue samples from patients diagnosed with follicular cell-derived thyroid neoplasia were included, and upon DNA-extraction and qualitative measurements 99 samples were eligible for amplicon-based next-generation-sequencing. Libraries were generated using the TruSeq Amplicon Cancer Panel, followed by sequencing using a MiSeq. Upon data processing and variant filtering all variants were manually assessed to exclude false positive mutations in the final curated list. Moreover, hot-spot mutations were validated using an independent platform from Agilent. Each diagnostic group were correlated to mutation burden and individual mutations were classified according to recent guidelines for somatic mutation classification. Close to 100% of the archived FFPE samples were eligible for DNA-library preparation and amplicon sequencing based on DNA quality criterion. The distribution of mutations in the specific diagnostic groups resulted in a higher mutation frequency among the most dedifferentiated than in the groups with a more differentiated cell profile. Based on the distribution mutations across the samples and using hierarchical clustering, we generated four tentative mutational signatures; highly mutated tumors; tumors with mainly NRAS and TP53 mutations; BRAF mutated tumors and tumors with none or single sporadic mutations. Future studies including more samples and follow-up data may amend these signatures, however our results imply that morphological classification of follicular cell derived thyroid neoplasia could be supplemented with a somatic mutational signature. Taken together, broad screening of the somatic alterations in FFPE tissue of thyroid neoplasia is comprehensible and essential for future identification of possible treatment targets and personalized medicine. (Copyright © 2020 Madsen, Kiss, Cilius Nielsen, Bennedbæk and Rossing.) |
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| فهرسة مساهمة: | Keywords: FFPE-preserved DNA; follicular cell-derived thyroid neoplasia; next-generation sequencing; somatic mutation profile; somatic variant classification |
| المشرفين على المادة: | 0 (Biomarkers, Tumor) 0 (DNA, Neoplasm) |
| تواريخ الأحداث: | Date Created: 20200409 Date Completed: 20210226 Latest Revision: 20210226 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC7105679 |
| DOI: | 10.3389/fendo.2020.00146 |
| PMID: | 32265839 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-2392 |
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| DOI: | 10.3389/fendo.2020.00146 |