【佳學(xué)基因靶向藥物基因檢測(cè)】涉及表觀遺傳調(diào)控基因和 RhoA GTPase 的腫瘤突變負(fù)荷可預(yù)測(cè)淋巴結(jié)成熟 T 細(xì)胞淋巴瘤的總體存活率

基因檢測(cè)號(hào)碼資源

深研組織分子診斷與基因分析明白《Clin Epigenetics》在?2022 Dec 19;14(1):180.發(fā)表了一篇題目為《》腫瘤靶向藥物治療基因檢測(cè)臨床研究文章。該研究由Luís Alberto de Pádua Covas Lage,?Hebert Fabrício Culler,?Guilherme Carneiro Barreto,?Cadiele Oliana Reichert,?Débora Levy,?Renata de Oliveira Costa,?Vanderson Rocha,?Juliana Pereira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。

腫瘤基因檢測(cè)及靶向藥物治療研究關(guān)鍵詞：

臨床結(jié)果,表觀遺傳學(xué),分子生物標(biāo)志物,淋巴結(jié)成熟 T 細(xì)胞淋巴瘤, RhoA突變。

腫瘤治療檢測(cè)基因臨床應(yīng)用結(jié)果

淋巴結(jié)成熟 T 細(xì)胞淋巴瘤 (nMTCL) 包括一組具有侵襲性生物學(xué)行為和不良預(yù)后的異質(zhì)性罕見(jiàn)惡性腫瘤。表觀遺傳現(xiàn)象，包括控制 DNA 甲基化和組蛋白去乙?；幕蛲蛔?，以及 RhoA GTPase 的失活突變，在其發(fā)病機(jī)制中起著核心作用，并構(gòu)成治療干預(yù)的潛在新靶點(diǎn)。腫瘤突變負(fù)荷 (TMB) 反映了克隆進(jìn)化的過(guò)程，預(yù)測(cè)了對(duì)抗癌治療的反應(yīng)，并已成為幾種實(shí)體腫瘤的預(yù)后生物標(biāo)志物；然而，其潛在的預(yù)后影響在 nMTCL 中仍然未知。在這項(xiàng)研究中，我們使用目標(biāo)面板對(duì)福爾馬林固定石蠟包埋 (FFPE) 診斷性腫瘤樣本進(jìn)行了 Sanger 測(cè)序，以搜索涉及 IDH-1/IDH-2、TET-2、DNMT3A 和 RhoA 基因的反復(fù)突變。 nMTCL 59例。我們新穎證明，高 TMB（定義為存在 ≥ 兩個(gè)涉及上述基因的突變）與接受 CHOP 樣方案治療的 nMTCL 患者的總生存期降低相關(guān)。此外，高 TMB 與大塊疾病、較低的總體反應(yīng)率和較高的死亡率相關(guān)。未來(lái)使用更大隊(duì)列的研究可能會(huì)驗(yàn)證我們的初步結(jié)果，這些結(jié)果表明 TMB 是與 nMTCL 不良預(yù)后相關(guān)的潛在分子生物標(biāo)志物。表觀遺傳學(xué)；分子生物標(biāo)志物；淋巴結(jié)成熟 T 細(xì)胞淋巴瘤； RhoA突變。

腫瘤發(fā)生與革命國(guó)際數(shù)據(jù)庫(kù)描述：

Nodal mature T-cell lymphomas (nMTCL) comprises a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena, including mutations in genes that control DNA methylation and histone deacetylation, in addition to inactivating mutations in the RhoA GTPase, play a central role in its pathogenesis and constitute potential new targets for therapeutic intervention. Tumor mutational burden (TMB) reflects the process of clonal evolution, predicts response to anti-cancer therapies and has emerged as a prognostic biomarker in several solid neoplasms; however, its potential prognostic impact remains unknown in nMTCL. In this study, we conducted Sanger sequencing of formalin-fixed paraffin-embedded (FFPE) diagnostic tumor samples using a target-panel to search for recurrent mutations involving the IDH-1/IDH-2, TET-2, DNMT3A and RhoA genes in 59 cases of nMTCL. For the first time, we demonstrated that high-TMB, defined by the presence of ≥ two mutations involving the aforementioned genes, was associated with decreased overall survival in nMTCL patients treated with CHOP-like regimens. Additionally, high-TMB was correlated with bulky disease, lower overall response rate, and higher mortality. Future studies using larger cohorts may validate our preliminary results that indicate TMB as a potential molecular biomarker associated with adverse prognosis in nMTCL.Keywords:?Clinical outcomes; Epigenetics; Molecular biomarkers; Nodal mature T-cell lymphomas; RhoA mutation.