Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF-1 genes induced by a chromosomal translocation involving bands 12q13 and 16p11.
This case report documents the first karyotypic, fluorescence in situ hybridization, and genetic analysis of an angiomatoid fibrous histiocytoma that arose and recurred in the arm of a 5.5-year-old girl. Complex rearrangements between chromosomes 2, 12, 16, and 17 were noted, as well as deletion in the long arm of chromosome 11. Flow cytometry revealed a normal cell population. The t(12;16) site was further investigated using reverse transcriptase-polymerase chain reaction. We found that the FUS (also known as TLS) gene from 16p11 combined with the ATF-1 gene from 12q13 to generate a chimeric FUS/ATF-1. The FUS gene is rearranged in the t(12;16)(q13;p11) that characterizes myxoid liposarcoma and in acute myeloid leukemia with t(16;21)(p11;q22), while the ATF-1 gene is rearranged in the t(12;22)(q13;q12) found recurrently in clear cell sarcomas (malignant melanoma of soft parts). Thus, the FUS/ATF-1 gene in angiomatoid fibrous histiocytoma is predicted to code for a protein that is very similar to the chimeric EWS/ATF-1 found in clear cell sarcoma.
Waters
B L
BL
University of Vermont, College of Medicine, Burlington, VT, USA.
Panagopoulos
I
I
Allen
E F
EF
D051697:Activating Transcription Factor 1; D000595:Amino Acid Sequence; D019677:Artificial Gene Fusion; D001483:Base Sequence; D002648:Child; D002881:Chromosomes, Human, Pair 12; D002885:Chromosomes, Human, Pair 16; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005260:Female; D006391:Hemangioma / Q000235:genetics*; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008969:Molecular Sequence Data; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins / Q000235:genetics*; D012983:Soft Tissue Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D051697:Activating Transcription Factor 1; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins; D014157:Transcription Factors