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

腫瘤基因檢測(cè)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(dǎo)的 MPNST 的定義特征》腫瘤靶向藥物治療基因檢測(cè)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(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測(cè)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(biāo)模型,肉瘤,腫瘤微環(huán)境。

腫瘤靶向治療基因檢測(cè)臨床應(yīng)用結(jié)果

腫瘤微環(huán)境在癌癥生物學(xué)中起著重要作用，但小鼠模型的遺傳背景會(huì)使腫瘤表型的解釋復(fù)雜化。更深入地了解菌株依賴性對(duì)遺傳相同腫瘤的腫瘤微環(huán)境的影響對(duì)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(shí)別這些相互作用。在這里，我們使用體細(xì)胞 CRISPR/Cas9 腫瘤發(fā)生方法來確定小鼠背景對(duì)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(xué)的影響。據(jù)我們所知，這是先進(jìn)項(xiàng)系統(tǒng)評(píng)估宿主菌株對(duì) 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(dá)和 IHC 分析確定了 CD4+ T 細(xì)胞浸潤和骨髓細(xì)胞群（包括 M2 巨噬細(xì)胞和肥大細(xì)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(duì)使用類似體內(nèi)基因編輯方法的未來研究的設(shè)計(jì)具有影響。

腫瘤發(fā)生與反復(fù)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.