Renal cell carcinoma represents a model for contemporary classification of solid tumors; however, unusual and unclassifiable cases exist and are not rare in children and young adults. The anaplastic lymphoma kinase (ALK) gene has recently been implicated in subsets of pulmonary, esophageal, breast, and colon cancers. These findings strengthen the importance of molecular classification of carcinomas across different organ sites, especially considering the evolving targeted anticancer therapies with ALK inhibitors. In the current study of six pediatric renal cell carcinomas, two cases exhibited structural karyotypic abnormalities involving the ALK locus on chromosomal band 2p23. Fluorescence in situ hybridization (FISH) studies were positive for an ALK rearrangement in one case, and subsequent 5 0 rapid amplification of cDNA ends analysis of this tumor revealed that the 3 0 portion of the ALK transcript encoding for the kinase domain was fused in frame to the 5 Keywords: ALK; FISH; fusion gene; renal cell carcinoma; translocation; VCL Renal cell carcinoma has an incidence of 209 000 cases per year and is responsible for 102 000 deaths worldwide annually. 1,2 Approximately 80% of all renal carcinoma cases are currently classified as clear cell, papillary, or chromophobe subtypes with discrete molecular abnormalities characteristic for each group. 2-7 Rare subtypes have also been defined by the 2004 World Health Organization classification and include collecting duct, multilocular cystic, mucinous tubular and spindle cell, medullary, and Xp11.2 translocation-and neuroblastoma-associated carcinomas; each of these subtypes constitutes B1% of all primary kidney epithelial tumors and the three latter subtypes are diagnosed predominantly in children. 8,9 Additional

Usher syndrome type III is an autosomal recessive disorder characterized by progressive sensorineural hearing loss, vestibular dysfunction, and retinitis pigmentosa. The disease gene was localized to 3q25 and recently was identified by positional cloning. In the present study, we have revised the structure of the USH3 gene, including a new translation start site, 5' untranslated region, and a transcript encoding a 232-amino acid protein. The mature form of the protein is predicted to contain three transmembrane domains and 204 residues. We have found four new disease-causing mutations, including one that appears to be relatively common in the Ashkenazi Jewish population. We have also identified mouse (chromosome 3) and rat (chromosome 2) orthologues, as well as two human paralogues on chromosomes 4 and 10.

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Chondroid lipoma, a rare benign adipose tissue tumor, may histologically resemble myxoid liposarcoma or extraskeletal myxoid chondrosarcoma, but is genetically distinct. In the current study, an identical reciprocal translocation, t(11;16)(q13;p13) was identified in three chondroid lipomas, a finding consistent with previous isolated reports. A fluorescence in situ hybridization (FISH)-based positional cloning strategy using a series of bacterial artificial chromosome (BAC) probe combinations designed to narrow the 16p13 breakpoint revealed MKL2 as the candidate gene. Subsequent 5′ RACE studies demonstrated C11orf95 as the MKL2 fusion gene partner. MKL/myocardin-like 2 (MKL2) encodes myocardin-related transcription factor B (MRTF-B) in a megakaryoblastic leukemia gene family, and C11orf95 (chromosome 11 open reading frame 95) is a hypothetical protein. Sequencing analysis of RT-PCR generated transcripts from all three chondroid lipomas defined the fusion as occurring between exons 5 and 9 of C11orf95 and MKL2, respectively. Dual-color breakpoint spanning probe sets custom-designed for recognition of the translocation event in interphase cells confirmed the anticipated rearrangements of the C11orf95 and MKL2 loci in all cases. The FISH and RT-PCR assays developed in this study can serve as diagnostic adjuncts for identification of this novel C11orf95-MKL2 fusion oncogene in chondroid lipoma.