Lack of HLA class I antigen expression by melanoma cells SK-MEL-33 caused by a reading frameshift in beta 2-microglobulin messenger RNA.
The lack of HLA class I antigen expression by the melanoma cell line SK-MEL-33 is caused by a unique lesion in beta 2-microglobulin (beta 2-mu). Sequencing of beta 2-mu mRNA detected a guanosine deletion at position 323 in codon 76 that causes a frameshift with a subsequent introduction of a stop codon at a position 54 base upstream of the normal position of the stop codon in the message. The loss of 18 amino acids and the change of 6 amino acids, including a cysteine at position 80 in the carboxy terminus of beta 2-mu, are likely to cause marked changes in the structure of the polypeptide. The latter may account for the inability of beta 2-mu to associate with HLA class I heavy chains and for its lack of reactivity with the anti-beta 2-mu mAb tested. HLA class I antigen expression on SK-MEL-33 cells was reconstituted after transfection with a wild-type B2m gene, therefore indicating that the abnormality of endogenous B2m gene is the only mechanism underlying lack of HLA class I antigen expression by SK-MEL-33 cells. The guanosine deletion in B2m gene was detected also in the melanoma tissue from which SK-MEL-33 cells had originated. Therefore, the molecular lesion identified in the SK-MEL-33 melanoma cell line is not caused by a mutation acquired during growth in vitro but is likely to reflect a somatic mutation during tumor progression.
Wang
Z
Z
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
Cao
Y
Y
Albino
A P
AP
Zeff
R A
RA
Houghton
A
A
Ferrone
S
S
D000368:Aged; D001483:Base Sequence; D016368:Frameshift Mutation; D017353:Gene Deletion; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000235:genetics*
D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D001613:beta 2-Microglobulin