Identification of anaplastic lymphoma kinase fusions in renal cancer

  title={Identification of anaplastic lymphoma kinase fusions in renal cancer},
  author={Emiko Sugawara and Yuki Togashi and Naoto Kuroda and Seiji Sakata and Satoko Hatano and Reimi Asaka and Takeshi Yuasa and Junji Yonese and Masanobu Kitagawa and Hiroyuki Mano and Yuichi Ishikawa and Kengo Takeuchi},
Several promising molecular‐targeted drugs are used for advanced renal cancers. However, complete remission is rarely achieved, because none of the drugs targets a key molecule that is specific to the cancer, or is associated with “oncogene addiction” (dependence on one or a few oncogenes for cell survival) of renal cancer. Recently, an anaplastic lymphoma kinase (ALK) fusion, vinculin‐ALK, has been reported in pediatric renal cell carcinoma (RCC) cases who have a history of sickle cell trait… 
Identification of anaplastic lymphoma kinase fusions in clear cell renal cell carcinoma
It is shown that enforced EML4-ALK expression could significantly promote in vitro proliferation, clonogenic colony formation and apoptosis resistance in HK2 immortalized normal renal tubal epithelial cells and their in vivo outgrowth when injected into immunocompromised nude mice.
Targeted inhibition in tumors with ALK dependency.
The clinicopathologic features of ALK-driven NSCLC, the clinical development ofALK inhibitors, and the genetic determinants of acquired resistance to ALK inhibition are among the topics covered in this review.
ALK-rearranged renal cell carcinomas in Polish population.
ALKoma: a cancer subtype with a shared target.
  • H. Mano
  • Medicine
    Cancer discovery
  • 2012
It is proposed that tumors carrying abnormal ALK as an essential growth driver be collectively termed "ALKoma," and a marked clinical efficacy with ALK inhibitors has already been shown for some of the tumors with AlK fusions.
Treating ALK-positive lung cancer—early successes and future challenges
Crizotinib, an orally bioavailable inhibitor of ALK, provides significant benefit for patients with ALK-positive (ALK+) NSCLC in association with characteristic, mostly mild, toxic effects, and this drug has been approved by the FDA for clinical use in this molecularly defined subgroup of lung cancer.
Gene fusions in non-small-cell lung cancer
This review will focus on relatively common gene fusions in NSCLC and effective screening procedures and establish a highly sensitive, specific and reproducible screening procedure.
Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology
The current understanding of ALK function in human cancer and the implications for tumour treatment are discussed.
ALK-positive cancer: still a growing entity.
This review summarizes the current state of knowledge concerning ALK-positive neoplasms, focusing on the clinical aspects of the subject.
Crizotinib — a new molecular targeted agent in the treatment of non-small-cell lung cancer
Treatment with crizotinib was associated with 62% of objective response rate in molecularly defined subgroup of patients, and final conclusions are subject to further III phase clinical trials.
Discovery Stories of RET Fusions in Lung Cancer: A Mini-Review
In this mini-review article, the discovery of REarrangement during Transfection fusions, the third kinase fusion gene in lung cancer, is briefly described.


Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer.
The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients, and the drug resulted in grade 1 or 2 gastrointestinal side effects.
Renal cell carcinoma with novel VCL–ALK fusion: new representative of ALK-associated tumor spectrum
The data identify the kidney as a new organ site for ALK-associated carcinomas and VCL as a novel ALK fusion partner and demonstrate the potential clinical utility of this approach for detecting VCL–ALK in routinely processed tissue.
Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
It is shown that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells.
EML4–ALK fusion transcript is not found in gastrointestinal and breast cancers
The data suggest that the EML4–ALK fusion transcript is not present in gastrointestinal or breast cancers and is specific to NSCLC.
Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor.
A sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) is reported in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without theALK translocation, which support the dependence of ALk-rearranged tumors on AlK-mediated signaling and suggest a therapeutic strategy for genomically identified patients with the aggressive form of this soft-tissue tumor.
ALK rearrangement in sickle cell trait‐associated renal medullary carcinoma
Coprecipitation of strongly tyrosine phosphorylated talins with the VCL‐ALK oncoprotein is demonstrated, suggesting that ALK oncogenic crossphosphorylation is mediated by interactions between neighboring VCL•ALK proteins on a talin scaffold.
EML4-ALK Fusion Is Linked to Histological Characteristics in a Subset of Lung Cancers
In the present first investigation of EML4-ALK fusion in a large study of lung cancers, an interesting histotype-genotype relationship is found and the fusion protein could be detected by immunohistochemistry, pointing to possible clinical applications.
Favorable response to crizotinib in three patients with echinoderm microtubule‐associated protein‐like 4–anaplastic lymphoma kinase fusion‐type oncogene‐positive non‐small cell lung cancer
Three cases harboring EML4‐ALK rearrangement who were enrolled in the crizotinib trial showed favorable responses to the ALK‐specific tyrosine kinase inhibitor.
Crizotinib in anaplastic large-cell lymphoma.
The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been shown to induce a response in lung cancers in which ALK is mutated. Crizotinib is also effective in anaplastic large-cell lymphoma,
EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues.
The results show that the causal role and value of EML4-ALK as a therapeutic target remain to be defined and that the EML3-ALK transcript cannot be regarded as a specific diagnostic tool for NSCLC.