The SSX-2 gene, which is involved in the t(X;18) translocation of synovial sarcomas, codes for the human tumor antigen HOM-MEL-40.
Using autologous serum for the serological analysis of recombinantly expressed clones (SEREX) from a cDNA derived from a human melanoma, several new melanoma antigens were identified that are immunogenic in the autologous host. Sequence analysis revealed that one of these antigens, HOM-MEL-40, was coded for by the SSX2 gene, which has recently been described to be involved in the t(X;18) translocation of human synovial sarcomas. Expression analysis performed by Northern blot and RT-PCR demonstrated the presence of HOM-MEL-40 transcripts in a significant proportion of human melanomas (50%), colon cancers (25 %), hepatocarcinomas (30%), and breast carcinoma (20%) but not in normal tissues except for testis. Sequence comparison with transcripts cloned from testis ruled out mutations in the melanoma-derived HOM-MEL-40. Antibodies against HOM-MEL-40 were found in 10 of 89 patients with melanoma, including 3 of 8 patients with HOM-MEL-40-positive tumors, but not in 41 apparently healthy controls. In view of the specific expression pattern and immunogenicity in cancer patients, HOM-MEL-40 holds promise as a target for immune interventions in a considerable population of patients with HOM-MEL-40-positive tumors.
Türeci
O
O
Medizinische Klinik und Poliklinik, Innere Medizin I, Universitätskliniken des Saarlands, Homburg, Germany.
Sahin
U
U
Schobert
I
I
Koslowski
M
M
Scmitt
H
H
Schild
H J
HJ
Stenner
F
F
Seitz
G
G
Rammensee
H G
HG
Pfreundschuh
M
M
D000951:Antigens, Neoplasm / Q000032:analysis / Q000097:blood / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000276:immunology; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000097:blood / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*
D000951:Antigens, Neoplasm