Case Report: Next generation sequencing identifies a NAB2-STAT6 fusion in Glioblastoma.
Case Report: Next generation sequencing identifies a NAB2-STAT6 fusion in Glioblastoma.
复制标题
DOI：
10.1186/s13000-016-0455-9
复制
发表时间：
2016-01-27
影响因子：
2.6
通讯作者：
Ramkissoon SH
中科院分区：
文献类型：
--
作者：
Diamandis P;Ferrer-Luna R;Huang RY;Folkerth RD;Ligon AH;Wen PY;Beroukhim R;Ligon KL;Ramkissoon SH
分子分析揭示了胶质母细胞瘤（GBM）的遗传亚型，包括具有IDH 1突变的肿瘤，这些突变可提高生存率并改善对标准治疗的反应。通过在常规临床实践中绘制脑肿瘤的遗传图谱，我们能够快速识别可靶向的遗传改变。一名29岁男性出现新发癫痫发作，提示神经影像学检查，结果显示右侧顶叶轴内5 cm病灶增强。他接受了次全切除术，病理检查发现胶质母细胞瘤伴核分裂、微血管增生和坏死。免疫组织化学（IHC）分析显示GFAP、OLIG 2和SOX 2的弥漫性表达与胶质细胞系肿瘤一致。肿瘤细胞对IDH 1（R132 H）呈阳性，对ATRX呈阴性。临床靶向外显子组测序（DFBWCC Oncopanel）鉴定了多种功能变体，包括IDH 1（p.R132H）、TP 53（p.Y126_splice）、ATRX（p.R1302fs*）、HNF 1A（p.R263H）和NF 1（p.H2592del）变体以及涉及NAB 2外显子3和STAT 6外显子18的NAB 2-STAT 6基因融合事件。阵列比较基因组杂交（aCGH）进一步揭示NAB 2和STAT 6的局灶性扩增。IHC分析显示强的异质性STAT 6核定位（在20%的肿瘤细胞中）。虽然NAB 2：STAT 6融合在孤立性纤维瘤（SFT）中很常见，但我们首次报告了新诊断的继发性GBM或任何其他非SFT的事件。我们的研究进一步强调了全面的基因组分析在识别患者特异性靶向突变和重排方面的价值。
Molecular profiling has uncovered genetic subtypes of glioblastoma (GBM), including tumors with IDH1 mutations that confer increase survival and improved response to standard-of-care therapies. By mapping the genetic landscape of brain tumors in routine clinical practice, we enable rapid identification of targetable genetic alterations. A 29-year-old male presented with new onset seizures prompting neuroimaging studies, which revealed an enhancing 5 cm intra-axial lesion involving the right parietal lobe. He underwent a subtotal resection and pathologic examination revealed glioblastoma with mitoses, microvascular proliferation and necrosis. Immunohistochemical (IHC) analysis showed diffuse expression of GFAP, OLIG2 and SOX2 consistent with a tumor of glial lineage. Tumor cells were positive for IDH1(R132H) and negative for ATRX. Clinical targeted-exome sequencing (DFBWCC Oncopanel) identified multiple functional variants including IDH1 (p.R132H), TP53 (p.Y126_splice), ATRX (p.R1302fs*), HNF1A (p.R263H) and NF1 (p.H2592del) variants and a NAB2-STAT6 gene fusion event involving NAB2 exon 3 and STAT6 exon 18. Array comparative genomic hybridization (aCGH) further revealed a focal amplification of NAB2 and STAT6. IHC analysis demonstrated strong heterogenous STAT6 nuclear localization (in 20 % of tumor cells). While NAB2:STAT6 fusions are common in solitary fibrous tumors (SFT), we report this event for the first time in a newly diagnosed, secondary-type GBM or any other non-SFT. Our study further highlights the value of comprehensive genomic analyses in identifying patient-specific targetable mutations and rearrangements.