错配修复缺陷胶质瘤,具有空间上不同的idh突变型和idh野生型成分,出现在Lynch综合征的背景下。

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2023-04-01 DOI:10.1101/mcs.a006280
Hao Tan, Caleb Nerison, Cooper Stateler, Stephen G Bowden, Ahmed M Raslan, Prakash Ambady, Ramon F Barajas, Matthew D Wood
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引用次数: 0

摘要

MLH1、MSH2、PMS2和MSH6的致病性突变破坏DNA错配修复机制,并在杂合状态下导致Lynch综合征,其典型特征是易患子宫内膜癌、卵巢癌、结肠直肠癌、胃癌、乳腺癌、血液学和软组织癌。很少,这些基因的种系致病性畸变与原发性中枢神经系统肿瘤的发生有关。我们报告了一位没有癌症病史的成年女性,她表现为多中心浸润性幕上胶质瘤,累及左侧前颞角和左侧中央前回。这些病变的外科治疗和神经病理/分子评估显示,在这些空间不同的疾病部位,异柠檬酸脱氢酶(IDH)状态和组织学分级不一致。MLH1基因(p.R217fs*12, c.r 648delt)的移码改变在两个病变中被发现,随后在血液样本的种系检测中被发现,与Lynch综合征一致。尽管患者的肿瘤具有不同的组织病理学特征和不同的IDH状态,但分子研究结果表明,颅内肿瘤的两个部位可能是由于潜在的单等位基因种系错配修复缺陷而发展起来的。该病例说明了多中心胶质瘤遗传特征的重要性,并强调了中枢神经系统胶质瘤中种系错配修复基因致病性改变的致癌潜力。
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Mismatch repair-deficient glioma with spatially distinct IDH-mutant and IDH-wild type components arising in the setting of Lynch syndrome.

Pathogenic mutations in MLH1, MSH2, PMS2, and MSH6 compromise DNA mismatch repair mechanisms and in the heterozygous state result in Lynch syndrome, which is typified by a predisposition to endometrial, ovarian, colorectal, gastric, breast, hematologic, and soft tissue cancers. Rarely, germline pathogenic aberrations in these genes are associated with the development of primary central nervous system tumors. We present a report of an adult female with no prior cancer history who presented with a multicentric, infiltrative supratentorial glioma involving both the left anterior temporal horn and left precentral gyrus. Surgical treatment and neuropathological/molecular evaluation of these lesions revealed discordant isocitrate dehydrogenase (IDH) status and histologic grade at these spatially distinct disease sites. A frameshift alteration within the MLH1 gene (p.R217fs*12, c.648delT) was identified in both lesions and subsequently identified in germline testing of a blood sample, consistent with Lynch syndrome. Despite distinct histopathologic features and divergent IDH status of the patient's tumors, the molecular findings suggest that both sites of intracranial neoplasia may have developed as a consequence of underlying monoallelic germline mismatch repair deficiency. This case illustrates the importance of characterizing the genetic profile of multicentric gliomas and highlights the oncogenic potential of germline mismatch repair gene pathogenic alterations within central nervous system gliomas.

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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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