ABSTRACT
Renal cell carcinomas (RCCs) represent a heterogeneous group of neoplasms, which differ in histological, pathologic and clinical characteristics. The tumors originate from different locations within the nephron and are accompanied by different recurrent (cyto)genetic anomalies. Recently, a novel subgroup of RCCs has been defined, i.e., the MiT translocation subgroup of RCCs. These tumors originate from the proximal tubule of the nephron, exhibit pleomorphic histological features including clear cell morphologies and papillary structures, and are found predominantly in children and young adults. In addition, these tumors are characterized by the occurrence of recurrent chromosomal translocations, which result in disruption and fusion of either the TFE3 or TFEB genes, both members of the MiT family of basic helix-loop-helix/leucine-zipper transcription factor genes. Hence the name MiT translocation subgroup of RCCs. In this review several features of this RCC subgroup will be discussed, including the molecular mechanisms that may underlie their development.
Subject(s)
Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Translocation, Genetic , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Carcinoma, Renal Cell/pathology , Gene Fusion , Humans , Kidney Neoplasms/pathology , Neoplasm Proteins/geneticsABSTRACT
The antiestrogen tamoxifen is important in the treatment of hormone-dependent breast cancer, although development of resistance is inevitable. To unravel the molecular mechanisms of antiestrogen resistance, a search for involved genes was initiated. Retrovirus-mediated insertional mutagenesis was applied to human ZR-75-1 breast cancer cells. Infected cells were subjected to tamoxifen selection and a panel of resistant cell clones was established. Screening for a common integration site resulted in the identification of a novel gene designated BCAR3. Transfer of this locus by cell fusion or transfection of the BCAR3 cDNA to ZR75-1 and MCF-7 cells induces antiestrogen resistance. BCAR3 represents a putative SH2 domain-containing protein and is partly homologous to the cell division cycle protein CDC48.
