FGF4 and INT2 oncogenes are amplified and expressed in Kaposi's sarcoma

Kaposi's sarcoma (KS) is a vascular tumor, the pathogenesis of which has be en suggested to include human herpesvirus 8 (HHV-8) as well as various cyto kines and growth factors. Very little is known about cytogenetic and molecu lar genetic changes in KS. We studied DNA copy number changes in KS and fou nd a recurrent gain at 11q13. We then analyzed the amplification and expres sion status of two known oncogenes, FGF4 and INT2, residing at 11q13, Compa rative genomic hybridization, interphase fluorescence in situ hybridization with yeast artificial chromosome probes containing FGF4 and INT2, and immu noperoxidase immunostaining with anti-FGF4 and -INT2 antibodies were used o n 12 KS samples. AU samples tested were shown by polymerase chain reaction to be HHV-8 positive. A recurrent gain at 11q13 was shown by comparative ge nomic hybridization in 4 of 10 cases studied. Of six cases studied by inter phase fluorescence irt situ hybridization, four showed a 3- to 4-fold ampli fication with the probes containing FGF4 and INT2, Expression of FGF4 and I NT2 was found in nine and three cases, respectively, of nine studied. Ampli fication and expression of these genes is particularly interesting in the c ontext of oncovirus involvement, because INT2 is a homolog of mouse int2, w hich causes mammary carcinoma in mice when activated by integration of retr ovirus mouse mammary tumor virus. This raises the question of whether HHV-8 represents an integrating oncovirus that causes amplification and activati on of genomic oncogenes in humans.