软组织肌上皮癌的全基因组特征。

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2022-12-01 DOI:10.1101/mcs.a006227
Joanna Cyrta, Joel Rosiene, Rohan Bareja, Sarah Kudman, Wael Al Zoughbi, Samaneh Motanagh, David C Wilkes, Kenneth Eng, Tuo Zhang, Evan Sticca, Susan Mathew, Mark A Rubin, Andrea Sboner, Olivier Elemento, Brian P Rubin, Marcin Imielinski, Juan Miguel Mosquera
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引用次数: 1

摘要

软组织肌上皮癌(myo上皮癌,mec)是一种罕见的侵袭性肿瘤,影响青少年和儿童,但其分子结构尚未通过基因组测序全面探索。在这里,我们介绍了两个mec的全外显子组测序(WES)、全基因组测序(WGS)和RNA测序结果。患者1和2 (P1, P2)均为男性,分别在27岁和37岁时被诊断为肩部(P1)和腹股沟(P2)软组织肿瘤。两名患者都出现了转移性疾病,P2死于疾病。P1肿瘤表现为横纹肌样细胞形态,INI1 (SMARCB1)表达完全缺失,与SMARCB1纯合子缺失相关。P2肿瘤呈透明细胞/小细胞形态,保留INI1表达,S100阳性。通过WES和WGS,两例患者的肿瘤均表现出较低的肿瘤突变负荷,未检测到可靶向的癌基因改变。P2的肿瘤包含EWSR1::KLF15重排,而来自P1的肿瘤显示新的ASCC2::GGNBP2融合。WGS证实了P1肿瘤中主要涉及17号和22号染色体的复杂基因组事件,这与嗜色性一致。这些发现与先前报道的MEC中EWSR1重排(50%的病例)一致,并为通过免疫组化在40%的MEC病例中10%观察到的SMARCB1蛋白表达缺失提供了遗传基础。在这些肿瘤中缺乏额外的驱动突变支持了这些改变是MEC进化中的关键分子事件的假设。此外,WES不可见的复杂结构变异模式的存在,突出了通过将WGS应用于罕见癌症可以获得的新的生物学见解。
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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Whole-genome characterization of myoepithelial carcinomas of the soft tissue.

Myoepithelial carcinomas (MECs) of soft tissue are rare and aggressive tumors affecting young adults and children, but their molecular landscape has not been comprehensively explored through genome sequencing. Here, we present the whole-exome sequencing (WES), whole-genome sequencing (WGS), and RNA sequencing findings of two MECs. Patients 1 and 2 (P1, P2), both male, were diagnosed at 27 and 37 yr of age, respectively, with shoulder (P1) and inguinal (P2) soft tissue tumors. Both patients developed metastatic disease, and P2 died of disease. P1 tumor showed a rhabdoid cytomorphology and a complete loss of INI1 (SMARCB1) expression, associated with a homozygous SMARCB1 deletion. The tumor from P2 showed a clear cell/small cell morphology, retained INI1 expression and strong S100 positivity. By WES and WGS, tumors from both patients displayed low tumor mutation burdens, and no targetable alterations in cancer genes were detected. P2's tumor harbored an EWSR1::KLF15 rearrangement, whereas the tumor from P1 showed a novel ASCC2::GGNBP2 fusion. WGS evidenced a complex genomic event involving mainly Chromosomes 17 and 22 in the tumor from P1, which was consistent with chromoplexy. These findings are consistent with previous reports of EWSR1 rearrangements (50% of cases) in MECs and provide a genetic basis for the loss of SMARCB1 protein expression observed through immunohistochemistry in 10% of 40% of MEC cases. The lack of additional driver mutations in these tumors supports the hypothesis that these alterations are the key molecular events in MEC evolution. Furthermore, the presence of complex structural variant patterns, invisible to WES, highlights the novel biological insights that can be gained through the application of WGS to rare cancers.

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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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