The discrimination between well-differentiated liposarcomas/atypical lipomatous tumors and lipomas can be diagnostically challenging at the histological level. However, cytogenetic identification of ring and giant rod chromosomes supports the diagnosis of well-differentiated liposarcoma/atypical lipomatous tumor. These abnormal chromosomes are mainly composed of amplified genomic sequences derived from chromosome 12q13-15, and contain several genes, including MDM2, CDK4 (SAS), TSPAN31, HMGA2, and others. MDM2 is consistently amplified in well-differentiated liposarcomas/atypical lipomatous tumors, and up to 25% in other sarcomas. As part of a large genomic study of lipomatous neoplasms, we initially found CPM to be consistently amplified in well-differentiated liposarcomas/atypical lipomatous tumors. To further explore this initial finding, we investigated the copy number status of MDM2 and CPM by fluorescent in situ hybridization (FISH) on a series of 138 tumors and 17 normal tissues, including 32 well-differentiated liposarcoma/atypical lipomatous tumors, 63 lipomas, 11 pleomorphic lipomas, 2 lipoblastomas, 30 other tumors and 17 normal fat samples. All 32 well-differentiated liposarcoma/atypical lipomatous tumors showed amplification of MDM2 and CPM, usually 420 copies per cell. The other tumors lacked MDM2 and/or CPM amplification. Chromogenic in situ hybridization confirmed the above results on a subset of these tumors (n ¼ 27). These findings suggest that identification of CPM amplification could be used as an alternative diagnostic tool for the diagnosis of welldifferentiated liposarcoma/atypical lipomatous tumors.

A child whose features are consistent with Pallister-Killian syndrome (PKS) did not have detectable tetrasomy 12p due to an additional isochromosome 12p in an unstimulated blood specimen by interphase FISH or array CGH analysis. The diagnosis of PKS was made through these methods solely in a skin biopsy specimen. To determine the sensitivity of our array CGH platform to tetrasomy 12p mosaicism, dilutions of DNA from both the child's skin fibroblasts and a PKS cell line were analyzed. Tetrasomy 12p at 10% mosaicism was identifiable but 5% was below the limit of detection. This result suggests through extrapolation that the tetrasomy 12p is present in <10% of cells in our patient's blood, confirming the tissue-limited mosaicism of PKS. Multiple recent studies show that array CGH provides greater sensitivity than chromosome analysis to detect mosaic abnormalities including that of tetrasomy 12p in blood specimens. However, our case demonstrates that the biology of PKS precludes the exclusive use of array CGH on blood for diagnosis. A tissue sample should continue to be the diagnostic gold standard for PKS.

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Lipoma is a benign tumor composed of mature adipocytes and one of the most common mesenchymal tumors seen in adults. Rearrangement of HMGA2 in chromosome band 12q15 has been found in approximately 60-70% of ordinary lipomas with cytogenetic abnormalities. Herein, we report two novel HMGA2 fusion sequences in lipomas with chromosome 12 rearrangements. Cytogenetic studies showed 12q abnormalities in both cases, and fluorescence in situ hybridization (FISH) confirmed the involvement of HMGA2 in each instance. Rapid amplification of cDNA ends (RACE) PCR experiments revealed that one lipoma contained a fusion of the HMGA2 3' untranslated region (UTR) to a genomic area downstream of the DYRK2 locus on 12q15; the second lipoma showed a fusion of the HMGA2 3' UTR to a genomic sequence upstream of the DCN locus on 12q21. In both instances the breakpoint on HMGA2 occurred downstream to let-7 miRNA (microRNA) consensus binding site (CBS) 1. These two and several other previously reported tumors containing HMGA2 3' UTR rearrangements show breakpoints after let-7 miRNA CBS 1, which suggests that the elimination of this miRNA binding site is not critical for driving HMGA2 transcriptional upregulation.

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