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

• Published in: Cancer genetics and cytogenetics 2000-09, Vol.121 (2), p.109-116
• Main Authors: Waters, Brenda L, Panagopoulos, Ioannis, Allen, Elizabeth F
• Format: Article
• Language: English
• Subjects: Activating Transcription Factor 1; Amino Acid Sequence; Artificial Gene Fusion; Base Sequence; Biological and medical sciences; Child; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 16; Dermatology; DNA, Complementary; DNA-Binding Proteins; Female; Hemangioma - genetics; Heterogeneous-Nuclear Ribonucleoproteins; Histiocytoma, Benign Fibrous - genetics; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Medical sciences; Molecular Sequence Data; Ribonucleoproteins - genetics; RNA-Binding Protein EWS; RNA-Binding Protein FUS; Soft Tissue Neoplasms - genetics; Transcription Factors - genetics; Translocation, Genetic; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0165-4608; 1873-4456
• DOI: 10.1016/S0165-4608(00)00237-5

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.