ALK as a paradigm of oncogenic promiscuity: different mechanisms of activation and different fusion partners drive tumors of different lineages

作者：Marino Enriquez Adrian; Dal Cin Paola^*

来源：Cancer Genetics, 2013, 206(11): 357-373.

DOI：10.1016/j.cancergen.2013.07.001

• ALK
• fusion proteins
• oncogene
• translocations
• receptor tyrosine kinase

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase protein implicated in a variety of hematological malignancies and solid tumors. Since the identification of the ALKgene in 1994 as the target of the t(2;5) chromosomal translocation in anaplastic large cell lymphoma, ALK has been proven a remarkably promiscuous oncogene. ALK contributes to the development of a notable assortment of tumor types from different lineages, including hematolymphoid, mesenchymal, epithelial and neural tumors, through a variety of genetic mechanisms: gene fusions, activating point mutations, and gene amplification. Recent developments led to significant diagnostic and therapeutic advances, including efficient diagnostic tests and ALK-targeting agents readily available in the clinical setting. This review addresses some therapeutic considerations of ALK-targeted agents and the biologic implications of ALK oncogenic promiscuity, but the main points discussed are: 1) the variety of mechanisms that result in activation of the ALK oncogene, with emphasis on the promiscuous partnerships demonstrated in chromosomal rearrangements; 2) the diversity of tumor types of different lineages in which ALK has been implicated as a pathogenic driver; and 3) the different diagnostic tests available to identify ALK-driven tumors, and their respective indications.

• 出版日期2013-11