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。

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2023-04-01 DOI:10.1101/mcs.a006257
Sylvain Mayeur, Benoit Lhermitte, Justine Gantzer, Anne Molitor, Tristan Stemmelen, Sébastien Meyer, Aline Kolmer, Jean-Emmanuel Kurtz, Seiamak Bahram, Raphael Carapito
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引用次数: 0

摘要

化疗后,纵隔生殖细胞肿瘤可导致成熟畸胎瘤,该畸胎瘤由来自所有三个生殖层的组织组成。虽然畸胎瘤通常是可以治愈的,但在极少数情况下,它可以产生各种躯体肿瘤,并且在特殊情况下,它会经历黑素细胞神经外胚层肿瘤(MNT)的转化,这一过程尚未得到很好的描述。我们报告了一位化疗后胸腺畸胎瘤合并MNT成分的患者,10年后,另外出现了与间变性MNT相对应的椎体转移。利用成熟畸胎瘤、MNT及其转移性椎体间变性MNT组分的外显子组测序,我们确定了至少两个组分共有的19个体细胞突变。这三种成分共有6个突变,其中3个位于已知的癌症相关基因KRAS (p.E63K)、TP53 (p.p p222x)和POLQ (p.S447P)。基因集富集分析发现,黑色素瘤发生通路中富集了4个主要驱动基因KRAS、TP53、ERBB4、KDR等突变基因,提示这些基因可能参与了畸胎瘤间变性MNT转化的发展。据我们所知,这是第一个在MNT上实现的分子研究。了解这些肿瘤的临床病理和分子特征对于更好地了解其发展和改善治疗方法至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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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.

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来源期刊
Cold Spring Harbor Molecular Case Studies
Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.20
自引率
0.00%
发文量
54
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.
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