title: Increased ALK1 copy number and renal cell carcinoma-a case report.
abstract: There have been recent reports of a rare variant of renal cell carcinoma associated with upregulation of the anaplastic lymphoma kinase gene (ALK) arising as a consequence of chromosomal translocations. The tumours were described as having a characteristic morphology. Here, we describe a case with similar morphology characterised by eosinophilic cells, abundant intracytoplasmic lumina and scattered large ganglion-like tumour cells. There was focal staining for ALK demonstrated by immunohistochemistry. However, rather than exhibiting a chromosomal translocation involving ALK, the use of FISH and a break-apart probe demonstrated that there was increased copy number of intact 2p23, the chromosomal region containing the ALK gene. Furthermore, the use of comparative genomic hybridisation showed increase of the whole of chromosome 2 along with chromosomes 6 and 17. There was no evidence of loss of 3p nor of trisomy of 7 associated with clear cell and papillary carcinoma, respectively. We suggest that this demonstrates a novel mechanism of upregulation of ALK activity by increased copy number occurring during the development of a renal carcinoma with the characteristic ALK-associated morphology.
authors: Cork University Hospital, Cork, Ireland.
authors: Ciara
authors: C
authors: Ryan
authors: Nick
authors: N
authors: Mayer
authors: Joan
authors: J
authors: Cunningham
authors: Gordon
authors: G
authors: Hislop
authors: Norman
authors: N
authors: Pratt
authors: Stewart
authors: S
authors: Fleming
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics*; D000328:Adult; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male
chemical_list: C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II