{"title":"作为纵隔生殖细胞肿瘤一部分的成熟胸腺畸胎瘤引起的转移性间变性黑素细胞神经外胚层肿瘤的基因组分析。","authors":"Sylvain Mayeur, Benoit Lhermitte, Justine Gantzer, Anne Molitor, Tristan Stemmelen, Sébastien Meyer, Aline Kolmer, Jean-Emmanuel Kurtz, Seiamak Bahram, Raphael Carapito","doi":"10.1101/mcs.a006257","DOIUrl":null,"url":null,"abstract":"<p><p>Following chemotherapy, a mediastinal germ cell tumor can lead to a mature teratoma that is composed of tissues derived from all three germ layers. Although teratoma is usually curable, in rare cases it can give rise to various somatic tumors and exceptionally it undergoes melanocytic neuroectodermal tumor (MNT) transformation, a process that is not well-described. We report a patient with a postchemotherapy thymic teratoma associated with an MNT component who, 10 years later, additionally presented a vertebral metastasis corresponding to an anaplastic MNT. Using exome sequencing of the mature teratoma, the MNT and its metastatic vertebral anaplastic MNT components, we identified 19 somatic mutations shared by at least two components. Six mutations were common to all three components, and three of them were located in the known cancer-related genes <i>KRAS</i> (p.E63K), <i>TP53</i> (p.P222X), and <i>POLQ</i> (p.S447P). Gene set enrichment analysis revealed that the melanoma tumorigenesis pathway was enriched in mutated genes including the four major driver genes <i>KRAS</i>, <i>TP53</i>, <i>ERBB4</i>, and <i>KDR</i>, indicating that these genes may be involved in the development of the anaplastic MNT transformation of the teratoma. To our knowledge, this is the first molecular study realized on MNT. Understanding the clinicopathological and molecular characteristics of these tumors is essential to better understand their development and to improve therapeutics.</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a2/59/MCS006257May.PMC10240838.pdf","citationCount":"0","resultStr":"{\"title\":\"Genomic profiling of a metastatic anaplastic melanocytic neuroectodermal tumor arising from a mature thymic teratoma as part of a mediastinal germ cell tumor.\",\"authors\":\"Sylvain Mayeur, Benoit Lhermitte, Justine Gantzer, Anne Molitor, Tristan Stemmelen, Sébastien Meyer, Aline Kolmer, Jean-Emmanuel Kurtz, Seiamak Bahram, Raphael Carapito\",\"doi\":\"10.1101/mcs.a006257\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Following chemotherapy, a mediastinal germ cell tumor can lead to a mature teratoma that is composed of tissues derived from all three germ layers. Although teratoma is usually curable, in rare cases it can give rise to various somatic tumors and exceptionally it undergoes melanocytic neuroectodermal tumor (MNT) transformation, a process that is not well-described. We report a patient with a postchemotherapy thymic teratoma associated with an MNT component who, 10 years later, additionally presented a vertebral metastasis corresponding to an anaplastic MNT. Using exome sequencing of the mature teratoma, the MNT and its metastatic vertebral anaplastic MNT components, we identified 19 somatic mutations shared by at least two components. Six mutations were common to all three components, and three of them were located in the known cancer-related genes <i>KRAS</i> (p.E63K), <i>TP53</i> (p.P222X), and <i>POLQ</i> (p.S447P). Gene set enrichment analysis revealed that the melanoma tumorigenesis pathway was enriched in mutated genes including the four major driver genes <i>KRAS</i>, <i>TP53</i>, <i>ERBB4</i>, and <i>KDR</i>, indicating that these genes may be involved in the development of the anaplastic MNT transformation of the teratoma. To our knowledge, this is the first molecular study realized on MNT. Understanding the clinicopathological and molecular characteristics of these tumors is essential to better understand their development and to improve therapeutics.</p>\",\"PeriodicalId\":10360,\"journal\":{\"name\":\"Cold Spring Harbor Molecular Case Studies\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2023-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a2/59/MCS006257May.PMC10240838.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cold Spring Harbor Molecular Case Studies\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/mcs.a006257\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cold Spring Harbor Molecular Case Studies","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/mcs.a006257","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Genomic profiling of a metastatic anaplastic melanocytic neuroectodermal tumor arising from a mature thymic teratoma as part of a mediastinal germ cell tumor.
Following chemotherapy, a mediastinal germ cell tumor can lead to a mature teratoma that is composed of tissues derived from all three germ layers. Although teratoma is usually curable, in rare cases it can give rise to various somatic tumors and exceptionally it undergoes melanocytic neuroectodermal tumor (MNT) transformation, a process that is not well-described. We report a patient with a postchemotherapy thymic teratoma associated with an MNT component who, 10 years later, additionally presented a vertebral metastasis corresponding to an anaplastic MNT. Using exome sequencing of the mature teratoma, the MNT and its metastatic vertebral anaplastic MNT components, we identified 19 somatic mutations shared by at least two components. Six mutations were common to all three components, and three of them were located in the known cancer-related genes KRAS (p.E63K), TP53 (p.P222X), and POLQ (p.S447P). Gene set enrichment analysis revealed that the melanoma tumorigenesis pathway was enriched in mutated genes including the four major driver genes KRAS, TP53, ERBB4, and KDR, indicating that these genes may be involved in the development of the anaplastic MNT transformation of the teratoma. To our knowledge, this is the first molecular study realized on MNT. Understanding the clinicopathological and molecular characteristics of these tumors is essential to better understand their development and to improve therapeutics.
期刊介绍:
Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.