Renal angiomyolipoma (AML) harboring a missense mutation of TSC2 with copy-neutral loss of heterozygosity (CN-LOH)
Renal angiomyolipoma (AML) harboring a missense mutation of TSC2 with copy-neutral loss of heterozygosity (CN-LOH)
复制标题
肾血管平滑肌脂肪瘤 (AML) 携带 TSC2 错义突变并伴有拷贝中性杂合性丢失 (CN-LOH)
DOI：
10.1080/15384047.2019.1702406
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发表时间：
2019
影响因子：
3.6
通讯作者：
Natori Hiroshi
中科院分区：
文献类型：
--
作者：
Idogawa Masashi;Hida Tokimasa;Tanaka Toshiaki;Ohira Noriaki;Tange Shoichiro;Sasaki Yasushi;Uhara Hisashi;Masumori Naoya;Tokino Takashi;Natori Hiroshi
血管平滑肌脂肪瘤（AML）被归类为血管周围上皮样细胞肿瘤，主要发生在肾脏。20%的肾AML患者患有由TSC 1或TSC 2基因的生殖系变异引起的结节性硬化综合征（TSC）。在本文中，我们报告了第一例肾AML携带体细胞错义突变的TSC 2基因和伴随的拷贝中性杂合性丢失（CN-LOH）。患者表现为孤立性肾AML和肺淋巴管肌瘤病，无其他提示TSC的结果。然而，肾AML的外显子组测序分析确定了TSC 2基因中的致病性体细胞错义突变（NM_000548：c.5228G>A：p.R1743Q），尽管没有检测到其他体细胞突变。此外，未检测到TSC 1或TSC 2的生殖系突变。有趣的是，突变等位基因比率对于没有杂合性丢失的体细胞杂合突变（洛）来说太高。此外，在TSC 2位点（16p13.3）附近未检测到拷贝数变异。为了阐明等位基因状态，我们分析了16号染色体上的杂合单核苷酸多态性（SNP）。在这些SNP中，不平衡的等位基因比率在16p13.3区域内积累。这些结果表明，拷贝中性洛（CN-洛）。因此，我们认为肾AML是由TSC 2基因的错义突变和TSC 2位点的CN-LOH引起的。
Angiomyolipoma (AML) is classified as a perivascular epithelioid cell neoplasm, mostly occurring in the kidney. Twenty percent of patients with renal AML have tuberous sclerosis complex (TSC) caused by germline variation in theTSC1orTSC2gene. In this paper, we report the first case of renal AML harboring somatic missense mutations of theTSC2gene and concomitant copy-neutral loss of heterozygosity (CN-LOH). The patient presented with solitary renal AML and pulmonary lymphangiomyomatosis and without other findings suggestive of TSC. Exome sequencing analysis of the renal AML, however, identified a pathogenic somatic missense mutation in theTSC2gene (NM_000548:c.5228G>A:p. R1743Q), although no other somatic mutation was detected. Furthermore, no germline mutation inTSC1orTSC2was detected. Interestingly, the mutant allele ratio was too high for a somatic heterozygous mutation without loss of heterozygosity (LOH). Furthermore, no copy number variation was detected around theTSC2locus (16p13.3). To clarify the allelic status, we analyzed heterozygous single-nucleotide polymorphisms (SNPs) in chromosome 16. In these SNPs, an unbalanced allele ratio was accumulated inside the 16p13.3 region. These results suggested copy-neutral LOH (CN-LOH). Consequently, we concluded that the missense mutation of theTSC2gene and CN-LOH of theTSC2locus caused renal AML.