ALK基因编码一种受体酪氨酸激酶(eceptor tyrosine kinase ,RTK),为跨膜蛋白,属于胰岛素受体超家族,在大脑发育与及特定的神经元中起重要作用。最初在间变性大细胞淋巴瘤(anaplastic large cell lymphoma, ALCL)发现ALK-NPM1融合蛋白,目前已在其它肿瘤中包括神经母细胞瘤和非小细胞肺癌,发现该基因出现突变、扩增或者重排,其中染色体重排最为常见,导致ALK与其他基因产生融合,包括ALK(2号染色体)/EML4(2号染色体),ALK / RANBP2(2号染色体),ALK /ATIC(2号染色体),ALK / TFG(3号染色体),ALK / NPM1(5号染色体),ALK / SQSTM1(5号染色体),ALK / KIF5B(10号染色体),ALK / CLTC(17号染色体),ALK / TPM4(19号染色体),和ALK / MSN(X染色体)。
在成神经细胞瘤中,F1245是三个高频率发现的热点ALK突变之一。在一个案例研究中,一个EML4-ALK F1245C突变的预处理非小细胞肺癌(NSCLC)患者在环唑替尼治疗过程中,在疾病进展缓慢后,对铈替尼的反应良好。尽管在环唑替尼治疗前并未对alk重排进行测序,但环唑替尼的耐药性归因于F1245C突变。患者在环唑替尼治疗期间疾病进展缓慢,反映了临床前的发现,表明与单纯融合相比,与F1245C融合的ALK对环唑替尼具有中度抵抗力。
In neuroblastoma, F1245 is one of three hotspot ALK mutations found at a high frequency. In a case study, a pretreated non-small cell lung cancer (NSCLC) patient with EML4-ALK F1245C mutation responded well to ceritinib after slow disease progression during crizotinib treatment. Crizotinib resistance was attributed to the F1245C mutation, although the ALK-rearrangement was not sequenced prior to crizotinib treatment. The patient's slow onset of disease progression during crizotinib treatment mirrors preclinical findings that indicate ALK-fusion with F1245C has moderate resistance to crizotinib compared to the fusion alone.
| Chr. | Start | Stop | Ref. s | Var. Bases |
| 2 | 29436859 | 29436859 | A | C |
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