Melanoma in a patient with DNMT3A overgrowth syndrome.
Melanoma in a patient with DNMT3A overgrowth syndrome.
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DOI：
10.1101/mcs.a006267
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发表时间：
2023-04
影响因子：
1.8
通讯作者：
Ley, Timothy J.
中科院分区：
文献类型：
--
作者：
Chen, David Y.;Sutton, Leslie A.;Ramakrishnan, Sai Mukund;Duncavage, Eric J.;Heath, Sharon E.;Compton, Leigh A.;Miller, Christopher A.;Ley, Timothy J.
表观遗传调节因子的改变越来越多地被认为是肿瘤发生的早期事件;因此，具有表观遗传调节因子获得性或遗传性变体的患者可能会增加患多种类型癌症的风险。DNMT 3A过度生长综合征（DOS）是由DNA甲基转移酶基因DNMT 3A的生殖系致病性变异引起的，与造血系统和神经系统恶性肿瘤的发生有关。已描述DNMT 3A缺乏促进小鼠中的角质形成细胞增殖。虽然改变的DNA甲基化模式在黑色素瘤中是公认的，但DNA甲基转移酶在黑色素瘤发病机制中的作用尚不清楚。我们报告的情况下，成年DOS患者与生殖系DNMT 3A功能丧失突变，谁开发了早发性黑色素瘤与区域淋巴结转移性疾病。原发性肿瘤的外显子组测序鉴定了显性肿瘤克隆中的额外获得性错义DNMT 3A突变，表明DNMT 3A功能的丧失与该肿瘤的发展相关。
Alterations in epigenetic regulators are increasingly recognized as early events in tumorigenesis; thus, patients with acquired or inherited variants in epigenetic regulators may be at increased risk for developing multiple types of cancer. DNMT3A overgrowth syndrome (DOS), caused by germline pathogenic variants in the DNA methyltransferase gene DNMT3A, has been associated with a predisposition toward development of hematopoietic and neuronal malignancies. DNMT3A deficiency has been described to promote keratinocyte proliferation in mice. Although altered DNA methylation patterns are well-recognized in melanoma, the role of DNA methyltransferases in melanoma pathogenesis is not clear. We report the case of an adult DOS patient with a germline DNMT3A loss-of-function mutation, who developed an early-onset melanoma with regional lymph node metastatic disease. Exome sequencing of the primary tumor identified an additional acquired, missense DNMT3A mutation in the dominant tumor clone, suggesting that the loss of DNMT3A function was relevant for the development of this tumor.
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作者：
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通讯作者：
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DOI：
10.1073/pnas.2022760118
发表时间：
2021-04-20
影响因子：
11.1
作者：
Chen DY;Ferguson IM;Braun KA;Sutton LA;Helton NM;Ramakrishnan SM;Smith AM;Miller CA;Ley TJ
通讯作者：
Ley TJ