【佳學基因檢測】不同的腫瘤微環(huán)境是菌株特異性 CRISPR/Cas9 誘導的 MPNST 的定義特征

腫瘤基因檢測公司排名解碼

探索看到《Genes (Basel)》在?2020 May 23;11(5):583發(fā)表了一篇題目為《不同的腫瘤微環(huán)境是菌株特異性 CRISPR/Cas9 誘導的 MPNST 的定義特征》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由Amanda Scherer?,?Victoria R Stephens?,?Gavin R McGivney?,?Wade R Gutierrez??,?Emily A Laverty?,?Vickie Knepper-Adrian?,?Rebecca D Dodd??等完成。促進了腫瘤的正確治療與個性化用藥的發(fā)展，進一步強調(diào)了基因信息檢測與分析的重要性。

腫瘤靶向藥物及正確治療臨床研究內(nèi)容關(guān)鍵詞：

CRISPR/Cas9, MPNST,鼠標模型,肉瘤,腫瘤微環(huán)境。

腫瘤靶向治療基因檢測臨床應(yīng)用結(jié)果

腫瘤微環(huán)境在癌癥生物學中起著重要作用，但小鼠模型的遺傳背景會使腫瘤表型的解釋復雜化。更深入地了解菌株依賴性對遺傳相同腫瘤的腫瘤微環(huán)境的影響對于探索基因型-表型關(guān)系至關(guān)重要，但使用傳統(tǒng)的 Cre/loxP 方法可能難以識別這些相互作用。在這里，我們使用體細胞 CRISPR/Cas9 腫瘤發(fā)生方法來確定小鼠背景對四種常用近交系中遺傳相同的惡性外周神經(jīng)鞘瘤 (MPNST) 生物學的影響。據(jù)我們所知，這是先進項系統(tǒng)評估宿主菌株對 CRISPR/Cas9 生成的小鼠模型影響的研究。我們的數(shù)據(jù)確定了多種菌株依賴性表型，包括腫瘤發(fā)作和免疫微環(huán)境的變化。雖然 BALB/c 小鼠比其他品系更早出現(xiàn) MPNST，但在 C57BL/6、129X1 和 129/SvJae 小鼠中觀察到類似的腫瘤發(fā)作。插入缺失模式分析表明，插入缺失的頻率、類型和大小在所有遺傳背景中都是相似的。基因表達和 IHC 分析確定了 CD4+ T 細胞浸潤和骨髓細胞群（包括 M2 巨噬細胞和肥大細胞）中的多種菌株依賴性差異。這些數(shù)據(jù)突出了基因組匹配的 MPNST 的重要菌株特異性表型，這些表型對使用類似體內(nèi)基因編輯方法的未來研究的設(shè)計具有影響。

腫瘤發(fā)生與反復轉(zhuǎn)移國際數(shù)據(jù)庫描述：

The tumor microenvironment plays important roles in cancer biology, but genetic backgrounds of mouse models can complicate interpretation of tumor phenotypes. A deeper understanding of strain-dependent influences on the tumor microenvironment of genetically-identical tumors is critical to exploring genotype-phenotype relationships, but these interactions can be difficult to identify using traditional Cre/loxP approaches. Here, we use somatic CRISPR/Cas9 tumorigenesis approaches to determine the impact of mouse background on the biology of genetically-identical malignant peripheral nerve sheath tumors (MPNSTs) in four commonly-used inbred strains. To our knowledge, this is the first study to systematically evaluate the impact of host strain on CRISPR/Cas9-generated mouse models. Our data identify multiple strain-dependent phenotypes, including changes in tumor onset and the immune microenvironment. While BALB/c mice develop MPNSTs earlier than other strains, similar tumor onset is observed in C57BL/6, 129X1 and 129/SvJae mice. Indel pattern analysis demonstrates that indel frequency, type and size are similar across all genetic backgrounds. Gene expression and IHC analysis identify multiple strain-dependent differences in CD4+ T cell infiltration and myeloid cell populations, including M2 macrophages and mast cells. These data highlight important strain-specific phenotypes of genomically-matched MPNSTs that have implications for the design of future studies using similar?in vivo?gene editing approaches.