Department of Medical Oncology, Adelaide and Meath Hospital, Dublin, Ireland.
Eur J Cancer. 2010 Sep;46(13):2357-68. doi: 10.1016/j.ejca.2010.04.006. Epub 2010 May 5.
The anaplastic lymphoma kinase gene (ALK) is a gene on chromosome 2p23 that has expression restricted to the brain, testis and small intestine but is not expressed in normal lymphoid tissue. It has similarity to the insulin receptor subfamily of kinases and is emerging as having increased pathologic and potential therapeutic importance in malignant disease. This gene was originally established as being implicated in the pathogenesis of rare diseases including inflammatory myofibroblastic tumour (IMT) and ALK-positive anaplastic large cell lymphoma, which is a subtype of non-Hodgkin's lymphoma. Recently the number of diseases in which ALK is implicated in their pathogenesis has increased. In 2007, an inversion of chromosome 2 involving ALK and a fusion partner gene in a subset of non-small cell lung cancer was discovered. In 2008, publications emerged implicating ALK in familial and sporadic cases of neuroblastoma, a childhood cancer of the sympatho-adrenal system. Chromosomal abnormalities involving ALK are translocations, amplifications or mutations. Chromosomal translocations are the longest recognised ALK genetic abnormality. When translocations occur a fusion gene is created between ALK and a gene partner. This has been described in ALK-positive anaplastic large cell lymphoma in which ALK is fused to NPM (nucleolar protein gene) and in non-small cell lung cancer where ALK is fused to EML4 (Echinoderm microtubule-associated protein 4). The most frequently described partner genes in inflammatory myofibroblastic tumour are tropomyosin 3/4 (TMP3/4), however in IMTs a diversity of ALK fusion partners have been found, with the ability to homodimerise a common characteristic. Point mutations and amplification of the ALK gene occur in the childhood cancer neuroblastoma. Therapeutic targeting of ALK fusion genes using tyrosine kinase inhibition, vaccination using an ALK specific antigen and treatment using viral vectors for RNAi are emerging potential therapeutic possibilities.
间变性淋巴瘤激酶基因（ALK）是染色体 2p23 上的一个基因，其表达仅限于脑、睾丸和小肠，但在正常淋巴组织中不表达。它与胰岛素受体亚家族激酶具有相似性，并且在恶性疾病中具有增加的病理和潜在治疗重要性。该基因最初被确定为参与罕见疾病的发病机制，包括炎症性肌纤维母细胞瘤（IMT）和 ALK 阳性间变性大细胞淋巴瘤，这是一种非霍奇金淋巴瘤的亚型。最近，ALK 参与其发病机制的疾病数量有所增加。2007 年，在一组非小细胞肺癌中发现了染色体 2 的倒位，涉及 ALK 和融合伙伴基因。2008 年，发表的文献表明 ALK 参与家族性和散发性神经母细胞瘤的发病机制，神经母细胞瘤是一种儿童交感肾上腺系统的癌症。涉及 ALK 的染色体异常包括易位、扩增或突变。染色体易位是最长的 ALK 遗传异常。当易位发生时，ALK 和一个基因伙伴之间会产生融合基因。在 ALK 阳性间变性大细胞淋巴瘤中，ALK 与 NPM（核仁蛋白基因）融合，在非小细胞肺癌中，ALK 与 EML4（Echinoderm microtubule-associated protein 4）融合，已经描述了这种情况。在炎症性肌纤维母细胞瘤中最常描述的伙伴基因是原肌球蛋白 3/4（TMP3/4），然而在 IMT 中已经发现了多种 ALK 融合伙伴，具有同源二聚化的共同特征。点突变和 ALK 基因的扩增发生在儿童癌症神经母细胞瘤中。针对 ALK 融合基因的治疗性靶向，使用酪氨酸激酶抑制、使用 ALK 特异性抗原的疫苗接种以及使用 RNAi 的病毒载体治疗，正在成为潜在的治疗可能性。
