ALK rearrangement in sickle cell trait‐associated renal medullary carcinoma

  title={ALK rearrangement in sickle cell trait‐associated renal medullary carcinoma},
  author={Adrian Mari{\~n}o-Enriquez and Wenbin Ou and Christopher B Weldon and Jonathan A. Fletcher and Antonio R. Perez-Atayde},
Renal Medullary Carcinoma (RMC) is an aggressive malignancy that affects young black individuals with sickle cell trait. No effective treatment is available, resulting in an ominous clinical course, with overall survival averaging less than four months. We report rearrangement of the ALK receptor tyrosine kinase in a pediatric case of RMC harboring a t(2;10)(p23;q22) translocation. Mass spectrometry‐based proteomic evaluation identified a novel ALK oncoprotein in which the cytoskeletal protein… 
VCL-ALK renal cell carcinoma in children with sickle-cell trait: the eighth sickle-cell nephropathy?
This neoplasm occurred in a young patient with sickle-cell trait and demonstrated distinctive morphologic features including medullary epicenter, discohesive polygonal or spindle-shaped cells with prominent cytoplasmic vacuoles, and prominent lymphocytic infiltrate.
ALK‐rearranged renal cell carcinomas in children
Based on the shared unique morphologic, immunophenotypic, and genetic features, it was proposed that these neoplasms belonged to a distinct subgroup of RCC frequently occurring in pediatric patients, which they have termed as ALK‐rearranged RCC.
ALK alterations in adult renal cell carcinoma: frequency, clinicopathologic features and outcome in a large series of consecutively treated patients
ALK rearrangement is rare in adult RCC but may be associated with distinct histological features and poor outcome, and another potential mechanism to elevate ALK expression, increased ALK gene copy number, was observed in 10% of adult CCRCC, where it is associated with a higher tumor grade and poorer outcome.
A review of ALK-rearranged renal cell carcinomas with a focus on clinical and pathobiological aspects.
Clinical and pathobiological aspects of ALK-RCC, a recently proposed and incorporated into the recent World Health Organisation Classification of renal tumours as a provisional entity, are reviewed with a focus on clinical and pathological aspects.
ALK-rearranged renal cell carcinomas in Polish population.
ALK-rearranged Renal Cell Carcinoma (RCC): A Report of 2 Cases and Review of the Literature Emphasizing the Distinction Between VCL-ALK and Non-VCL-ALK RCC
It was found that solid architecture and cytoplasmic vacuoles were present significantly more frequently in VCL-alk RCC than in non-VCL-ALK RCC, supporting the distinctive nature of the former.


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.
Activating mutations in ALK provide a therapeutic target in neuroblastoma
Neuroblastoma, an embryonal tumour of the peripheral sympathetic nervous system, accounts for approximately 15% of all deaths due to childhood cancer. High-risk neuroblastomas are rapidly
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.
TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors.
A new subtype of large B-cell lymphoma expressing the ALK kinase and lacking the 2; 5 translocation.
Seven cases of large B-cell lymphoma which define a previously unrecognized subgroup are reported, comprised of monomorphic large immunoblast-like cells, containing large central nucleoli, which tend to invade lymphatic sinuses.
Identification of ALK as a major familial neuroblastoma predisposition gene
It is demonstrated that heritable mutations of ALK are the main cause of familial neuroblastoma, and that germline or acquired activation of this cell-surface kinase is a tractable therapeutic target for this lethal paediatric malignancy.
Renal Medullary Carcinoma The Seventh Sickle Cell Nephropathy
It is concluded that renal medullary carcinoma represents another example of renal disease associated with sickle cell disorders, and the other six are unilateral hematuria, papillary necrosis, nephrotic syndrome, renal infarction, inability to concentrate urine, and pyelonephritis.
Proteomic identification of oncogenic chromosomal translocation partners encoding chimeric anaplastic lymphoma kinase fusion proteins.
The ability of mass spectrometry to identify oncogenic chimeric proteins resulting from chromosomal rearrangements can be adapted for the identification of known and unknown translocation partners of chimeric ALK fusion proteins involved in oncogenesis.
Oncogenic mutations of ALK kinase in neuroblastoma
It is demonstrated that downregulation of ALK through RNA interference suppresses proliferation of neuroblastoma cells harbouring mutated ALK, and that ALK-specific kinase inhibitors might improve its clinical outcome.