本文根據(jù)NCG(分析腫瘤基因的可重復性、同源性和網(wǎng)絡(luò)特性)提供的信息，列出了與多發(fā)性骨髓瘤相關(guān)的部分蛋白。

本文介紹了參與多發(fā)性骨髓瘤發(fā)病機制的幾個關(guān)鍵靶點，包括：

● ALOX12(花生四烯酸鹽12-脂氧合酶，12S型)作用于不同的多不飽和脂肪酸底物，產(chǎn)生具有生物活性的脂質(zhì)介質(zhì)，包括二十碳烷和脂氧素。在炎癥和氧化[7]中起重要作用。ALOX12的DNA異常甲基化和遺傳變異與人類多種疾病和病理表型相關(guān)。ALOX12 rs1126667和rs434473與[8]治療多發(fā)性骨髓瘤患者早期周圍神經(jīng)病變顯著相關(guān)。

● 細胞周期蛋白D1 (CCND1)參與細胞周期的正常調(diào)節(jié)和腫瘤形成。融合、重排、錯義突變、無義突變、沉默突變以及框內(nèi)缺失和插入可在癌癥中觀察到。Eman M. sewiify等報道在多發(fā)性骨髓瘤 ^[9]患者中，cyclin D1基因擴增與疾病嚴重程度、不良預后以及MDR1表達增加相關(guān)。

● DIS3 (DIS3 Homolog, Exosome Endoribonuclease And 3'-5' Exoribonuclease)是一種與酵母蛋白Rrp44同源的RNA酶，可作為真核細胞細胞核內(nèi)外泌體復合體的一部分。DIS3同時具有3'-5'核酸外切酶和核酸內(nèi)切酶活性。DIS3是多發(fā)性骨髓瘤中最常見的突變基因之一，其突變熱點與功能 ^[10]的變化一致。

● FAM46C (family with sequence similarity 46，成員C)是一種多聚A (A)聚合酶，與FAM46蛋白FAM46A、FAM46A和fam46d屬于核苷酸轉(zhuǎn)移酶超家族 ^[11]。它是多發(fā)性骨髓瘤中最常見的突變基因之一 ^[12]。FAM46C的功能喪失通過內(nèi)質(zhì)網(wǎng)反應(yīng)轉(zhuǎn)錄物的不穩(wěn)定驅(qū)動多發(fā)性骨髓瘤。FAM46C突變通過擾亂漿細胞分化和內(nèi)質(zhì)網(wǎng)穩(wěn)態(tài)促進骨髓瘤發(fā)病和疾病進展。

● MAGED1（黑色素瘤相關(guān)抗原D1）是MAGE同源結(jié)構(gòu)域（MHD）蛋白超家族的成員之一。MAGED1在發(fā)育和成年組織中普遍表達，但在大腦中特別豐富 ^[13]。Venkata D Yellapantula等人報道了使用全基因組測序和全外顯子組測序初步鑒定的9個頻繁突變基因列表，包括NRAS、KRAS、TP53、PNRC1、MAGED1、FAM46C、DIS3、CCND1和ALOX12B ^[14]。

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