| Abstract: |
Low-grade fibromyxoid sarcoma (LGFMS) is an indolent, late-metastasizing malignant soft-tissue tumor that is often mistaken for either more benign or more malignant tumor types. Cytogenetic analyses have identified a recurrent balanced translocation t(7;16) (q32-34;p11), later shown by molecular genetic approaches to result in a FUS/CREB3L2 fusion gene. Whereas preliminary studies suggest that this gene rearrangement is specific for LGFMS, its incidence in this tumor type and the possible existence of variant fusion genes have not yet been addressed. For this purpose, a series of potential LGFMS were obtained from nine different soft-tissue tumor centres and subjected to molecular analysis as well as careful histopathologic review. Reverse transcriptase-polymerase chain reaction analysis disclosed a FUS/CREB3L2 fusion transcript in 22 of the 23 (96%) cases that remained classified as LGFMS after the histologic re-evaluation and from which RNA of sufficient quality could be extracted, whereas none of the cases that were classified as other tumor types was fusion-positive. In one of the tumors with typical LGFMS appearance, we found that FUS was fused to the CREB3L1 gene instead of CREB3L2. The proteins encoded by these genes both belong to the same basic leucine-zipper family of transcription factors, and display extensive sequence homology in their DNA-binding domains. Thus, it is expected that the novel FUS/CREB3L1 chimera will have a similar impact at the cellular level as the much more common FUS/CREB3L2 fusion protein. Taken together, the results indicate that virtually all LGFMS are characterized by a chimeric FUS/CREB3L2 gene, and that rare cases may display a variant FUS/CREB3L1 fusion. © 2005 USCAP, Inc All rights reserved. |
| Keywords: |
adolescent; adult; child; human tissue; aged; middle aged; unclassified drug; dna binding protein; histopathology; protein domain; gene; metastasis; reverse transcription polymerase chain reaction; diagnosis, differential; tumor markers, biological; nerve tissue proteins; genetic variability; gene product; transcription factor; transcription factors; chimera; molecular cloning; gene rearrangement; amino acid sequence; molecular sequence data; hybrid protein; fibrosarcoma; recombinant fusion proteins; reverse transcriptase polymerase chain reaction; fusion gene; malignant neoplastic disease; chromosome translocation; base sequence; translocation, genetic; sequence homology; protein family; chromosome analysis; soft tissue neoplasms; soft tissue tumor; rt-pcr; cyclic amp response element-binding protein; rna analysis; rna-binding protein fus; chromosomes, human, pair 16; leucine zipper protein; chromosomes, human, pair 7; low-grade fibromyxoid sarcoma; fus/creb3l1; fus/creb3l2; fus creb3l1 protein; fus creb3l2 protein; creb3l2 gene; fus creb3l1 gene; fus creb3l2 gene; low grade fibromyxoid sarcoma
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