【佳學(xué)基因檢測】NF1微缺失患者的非編碼RNA ANRIL和叢狀神經(jīng)纖維瘤的數(shù)量

基因變異引起的叢狀神經(jīng)纖維瘤的原理

學(xué)習(xí)腫瘤基因檢測全面性的標(biāo)準(zhǔn)與實(shí)施方案記錄，得知《BMC Med Genet》在. 2012 Oct 26;13:98.發(fā)表了一篇題目為《NF1微缺失患者的非編碼RNA ANRIL和叢狀神經(jīng)纖維瘤的數(shù)量》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由Tanja Mußotter, Lan Kluwe, Josef Högel, Rosa Nguyen, David N Cooper, Victor-Felix Mautner, Hildegard Kehrer-Sawatzki等完成。促進(jìn)了叢狀神經(jīng)纖維瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測與分析在叢狀神經(jīng)纖維瘤的早期檢測與個(gè)性化治療的重要性。

腫瘤靶向藥物及正確治療臨床研究內(nèi)容關(guān)鍵詞：

NF1,微缺失，非編碼RNA，ANRIL,叢狀神經(jīng)纖維瘤,基因檢測

腫瘤靶向治療基因檢測臨床應(yīng)用結(jié)果

基因解碼基因檢測的研究介紹：1 型神經(jīng)纖維瘤病 (NF1) 是由 17q11.2 的 NF1 基因突變引起的，可以通過基因檢測進(jìn)行分析和遺傳阻斷。在 95% 的初始突變引起的 NF1 患者中，NF1 突變可以通過綜合突變分析基因檢測來識(shí)別。這些患者中有 5-10% 存在包含 NF1 基因及其側(cè)翼區(qū)域的微缺失。 NF1 的特征在于周圍神經(jīng)鞘的腫瘤，即特征性神經(jīng)纖維瘤。已觀察到該疾病的表征的出現(xiàn)在家族間和家族內(nèi)有相當(dāng)大的差異，這受與構(gòu)成性 NF1 突變無關(guān)的遺傳修飾因子的影響。 NF1 患者中叢狀神經(jīng)纖維瘤 (PNF) 的數(shù)量是一種高度可遺傳的遺傳特征。賊近，在基于家族的關(guān)聯(lián)研究中，SNP rs2151280 位于非編碼 RNA 基因 ANRIL 的 9p21.3 內(nèi)，被確定為與叢狀神經(jīng)纖維瘤數(shù)密切相關(guān)。與 ANRIL 表達(dá)降低相關(guān)的 rs2151280 的 T 等位基因似乎與更高的叢狀神經(jīng)纖維瘤數(shù)相關(guān)。 ANRIL 直接與 SUZ12 蛋白結(jié)合，該蛋白是多梳抑制復(fù)合物 2 的重要組成部分，是 SUZ12 占據(jù) CDKN2A/CDKN2B 腫瘤抑制基因及其表觀遺傳沉默所必需的?；蚪獯a基因檢測的研究方法：在這里，基因解碼基因檢測探索了叢狀神經(jīng)纖維瘤的潛在關(guān)聯(lián)使用正確的 Cochran-Armitage 趨勢檢驗(yàn)和正確的 Mann-Whitney-Wilcoxon 檢驗(yàn)，在 29 名患有組成性 NF1 微缺失的患者中使用 SNP rs2151280 的數(shù)量和叢狀神經(jīng)纖維瘤體積。這 29 名 NF1 患者的叢狀神經(jīng)纖維瘤數(shù)量和總腫瘤體積均通過全身 MRI 進(jìn)行評估。在這 29 名患者中觀察到的 NF1 微缺失包括 NF1 基因及其側(cè)翼區(qū)域，包括 SUZ12 基因?；蚪獯a基因檢測的研究結(jié)果：在研究的 29 名微缺失患者中，未發(fā)現(xiàn)叢狀神經(jīng)纖維瘤數(shù)量和叢狀神經(jīng)纖維瘤體積與 T 等位基因相關(guān)rs2151280. 基因解碼基因檢測的研究結(jié)論：基因解碼基因檢測的研究基因解碼基因檢測的研究結(jié)果表明，至少在 NF1 微缺失患者中，叢狀神經(jīng)纖維瘤易感性與 rs2151280 無關(guān)。盡管 NF1 野生型等位基因的體細(xì)胞失活被認(rèn)為是具有基因內(nèi)突變的 NF1 患者和具有 NF1 微缺失的患者的 PNF 起始事件，但由于存在 SUZ12 的雜合體結(jié)構(gòu)缺失，兩個(gè)患者組在腫瘤進(jìn)展方面可能不同僅適用于 NF1 微缺失患者。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國際數(shù)據(jù)庫描述：

Background: Neurofibromatosis type-1 (NF1) is caused by mutations of the NF1 gene at 17q11.2. In 95% of non-founder NF1 patients, NF1 mutations are identifiable by means of a comprehensive mutation analysis. 5-10% of these patients harbour microdeletions encompassing the NF1 gene and its flanking regions. NF1 is characterised by tumours of the peripheral nerve sheaths, the pathognomonic neurofibromas. Considerable inter- and intra-familial variation in expressivity of the disease has been observed which is influenced by genetic modifiers unrelated to the constitutional NF1 mutation. The number of plexiform neurofibromas (PNF) in NF1 patients is a highly heritable genetic trait. Recently, SNP rs2151280 located within the non-coding RNA gene ANRIL at 9p21.3, was identified as being strongly associated with PNF number in a family-based association study. The T-allele of rs2151280, which correlates with reduced ANRIL expression, appears to be associated with higher PNF number. ANRIL directly binds to the SUZ12 protein, an essential component of polycomb repressive complex 2, and is required for SUZ12 occupancy of the CDKN2A/CDKN2B tumour suppressor genes as well as for their epigenetic silencing.Methods: Here, we explored a potential association of PNF number and PNF volume with SNP rs2151280 in 29 patients with constitutional NF1 microdeletions using the exact Cochran-Armitage test for trends and the exact Mann-Whitney-Wilcoxon test. Both the PNF number and total tumour volume in these 29 NF1 patients were assessed by whole-body MRI. The NF1 microdeletions observed in these 29 patients encompassed the NF1 gene as well as its flanking regions, including the SUZ12 gene.Results: In the 29 microdeletion patients investigated, neither the PNF number nor PNF volume was found to be associated with the T-allele of rs2151280.Conclusion: Our findings imply that, at least in patients with NF1 microdeletions, PNF susceptibility is not associated with rs2151280. Although somatic inactivation of the NF1 wild-type allele is considered to be the PNF-initiating event in NF1 patients with intragenic mutations and patients with NF1 microdeletions, both patient groups may differ with regard to tumour progression because of the heterozygous constitutional deletion of SUZ12 present only in patients with NF1 microdeletions.