Distribution and favorable prognostic implication of genomic EGFR alterations in IDH-wildtype glioblastoma.
Distribution and favorable prognostic implication of genomic EGFR alterations in IDH-wildtype glioblastoma.
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DOI：
10.1002/cam4.4939
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发表时间：
2023-01
期刊：
影响因子：
4
通讯作者：
Yoshimoto, Koji
中科院分区：
文献类型：
--
作者：
Higa, Nayuta;Akahane, Toshiaki;Hamada, Taiji;Yonezawa, Hajime;Uchida, Hiroyuki;Makino, Ryutaro;Watanabe, Shoji;Takajo, Tomoko;Yokoyama, Seiya;Kirishima, Mari;Matsuo, Kei;Fujio, Shingo;Hanaya, Ryosuke;Tanimoto, Akihide;Yoshimoto, Koji
我们旨在评估异柠檬酸脱氢酶（IDH）‐野生型胶质母细胞瘤（GBMs）中表皮生长因子受体（EGFR）基因的突变谱、转录变异和预后影响。我们对EGFR进行了测序，使用下一代测序技术评估了EGFR剪接谱，并分析了138例IV级IDH野生型GBM病例的结果。在10%的GBMs中观察到EGFR突变。共有23.9%的GBMs出现EGFR扩增。此外，25%的EGFR突变发生在激酶结构域。值得注意的是，EGFR改变是良好预后的预测因子（p = 0.035）。与没有EGFR改变的GBM相比，EGFR改变的GBM与更高的Karnofsky绩效量表评分（p = 0.014）和更低的Ki - 67评分（p = 0.005）相关。EGFRvIII阳性在21%的EGFR扩增GBMs中检测到。我们在GBM病例中发现了另外两个EGFR变异，外显子6-7 （Δe 6-7）和外显子2-14 （Δe 2-14）缺失。在一个病例中，最初的EGFRvIII突变在复发期间转化为EGFR Δe 2-14突变。我们发现GBM的EGFR基因谱在不同的队列中存在差异，EGFR改变是IDH -野生型GBM患者总生存期的良好预后指标。此外，我们发现了EGFRvIII纵向和时间转化的罕见EGFR变异。在我们的队列中，表皮生长因子受体（EGFR）突变的频率很低，但在异柠檬酸脱氢酶野生型胶质母细胞瘤（GBMs）中，激酶结构域的EGFR突变频率很高。值得注意的是，在本研究中，有EGFR改变的GBM比没有改变的GBM有更好的预后。
We aimed to evaluate the mutation profile, transcriptional variants, and prognostic impact of the epidermal growth factor receptor (EGFR) gene in isocitrate dehydrogenase (IDH)‐wildtype glioblastomas (GBMs). We sequenced EGFR, evaluated the EGFR splicing profile using a next‐generation sequencing oncopanel, and analyzed the outcomes in 138 grade IV IDH‐wildtype GBM cases. EGFR mutations were observed in 10% of GBMs. A total of 23.9% of the GBMs showed EGFR amplification. Moreover, 25% of the EGFR mutations occurred in the kinase domain. Notably, EGFR alterations were a predictor of good prognosis (p = 0.035). GBM with EGFR alterations was associated with higher Karnofsky Performance Scale scores (p = 0.014) and lower Ki‐67 scores (p = 0.005) than GBM without EGFR alterations. EGFRvIII positivity was detected in 21% of EGFR‐amplified GBMs. We identified two other EGFR variants in GBM cases with deletions of exons 6–7 (Δe 6–7) and exons 2–14 (Δe 2–14). In one case, the initial EGFRvIII mutation transformed into an EGFR Δe 2–14 mutation during recurrence. We found that the EGFR gene profiles of GBM differ among cohorts and that EGFR alterations are good prognostic markers of overall survival in patients with IDH‐wildtype GBM. Additionally, we identified rare EGFR variants with longitudinal and temporal transformations of EGFRvIII. The frequency of epidermal growth factor receptor (EGFR) mutations was low but the frequency of EGFR mutations in the kinase domain was high in isocitrate dehydrogenase‐wildtype glioblastomas (GBMs) in our cohort. Notably, in this study, GBM with EGFR alterations had a better outcome than GBM without them.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
28.2
作者：
Francis JM;Zhang CZ;Maire CL;Jung J;Manzo VE;Adalsteinsson VA;Homer H;Haidar S;Blumenstiel B;Pedamallu CS;Ligon AH;Love JC;Meyerson M;Ligon KL
通讯作者：
Ligon KL
影响因子：
11.5
作者：
Batchelor, TT;Betensky, RA;Louis, DN
通讯作者：
Louis, DN
影响因子：
3.9
作者：
Adachi, Jun-ichi;Mishima, Kazuhiko;Nishikawa, Ryo
通讯作者：
Nishikawa, Ryo
影响因子：
11.5
作者：
Felsberg, Joerg;Hentschel, Bettina;Weller, Michael
通讯作者：
Weller, Michael