Dingani Nkosi, Andrew W Allbee, Paul G Rothberg, Jonathan W Friedberg, Andrew G Evans
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引用次数: 0
摘要
根据人类原发性恶性肿瘤的研究结果,有人提出一种以上不同的血淋巴肿瘤可能来自一个共同的突变干细胞或前体细胞。特别是血管免疫母细胞性T细胞淋巴瘤(AITL),它与其他造血恶性肿瘤具有共同的体细胞突变特征,有报道称它与髓样瘤或克隆性B细胞增生同时发生,相同的突变发生在多个细胞系中。在此,我们报告了这样一例病例:一名老年妇女在 8 年时间里被诊断出患有弥漫大 B 细胞淋巴瘤、多血质vera 和 AITL,每种疾病都在多个基因中存在相同的体细胞突变。总体而言,多个标本中至少有五个相同的核苷酸突变,其中两个相同的突变以不同的变异等位基因频率共同出现在所有三种标本类型中。这些发现证实了一个共同的突变干细胞可通过平行的造血分化途径产生多种肿瘤的理论。
Common clonal origin of three distinct hematopoietic neoplasms in a single patient: B-cell lymphoma, T-cell lymphoma, and polycythemia vera.
The potential for more than one distinct hematolymphoid neoplasm to arise from a common mutated stem or precursor cell has been proposed based on findings in primary human malignancies. Particularly, angioimmunoblastic T-cell lymphoma (AITL), which shares a somatic mutation profile in common with other hematopoietic malignancies, has been reported to occur alongside myeloid neoplasms or clonal B-cell proliferations, with identical mutations occurring in more than one cell lineage. Here we report such a case of an elderly woman who was diagnosed over a period of 8 years with diffuse large B-cell lymphoma, polycythemia vera, and AITL, each harboring identical somatic mutations in multiple genes. Overall, at least five identical nucleotide mutations were shared across multiple specimens, with two identical mutations co-occurring at variable variant allele frequencies in all three specimen types. These findings lend credence to the theory that a common mutated stem cell could give rise to multiple neoplasms through parallel hematopoietic differentiation pathways.
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.