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ß₂-Microglobulin Gene Is Mutated in a Human Colon Cancer Cell Line (HCT) Deficient in the Expression of HLA Class I Antigens on the Cell Surface¹

Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts 02111

The human colon cancer cell line HCT does not express any detectable HLA class I antigens on the cell surface. RNA blot analyses showed that HCT cells synthesize easily detectable levels of heavy chains as well as ß₂-microglobulin (ß₂m) transcripts. Experiments of immunoprecipitation revealed the presence of intracellular HLA heavy chains and the absence of ß₂m molecules. Sequencing studies, performed on polymerase chain reaction-mediated amplification of ß₂m-specific complementary DNAs, indicated that in HCT cells both ß₂m genes are mutated. The first mutation consists of an 11-base deletion, corresponding to the first 11 base pairs of the second exon of the ß₂m gene. This mutation alters the reading frame, starting from the third amino acid residue of the mature ß₂m protein, resulting in the synthesis of a 31-amino acid peptide with no remarkable homology to any of the sequences stored in the protein database. The second mutation is a point mutation (C A), resulting in a UAA stop codon corresponding to the 10th amino acid residue of the mature ß₂m. Therefore, it would appear that in HCT cells the ß₂m genes have undergone two different mutational changes. This is the first molecular demonstration of ß₂m mutations in a human epithelial cell line.

¹ This work was supported by grants from the NIH.

² To whom requests for reprints should be addressed, at Department of Radiation Oncology, New England Medical Center, Box 824, 750 Washington St., Boston, MA 02111.

Received 8/ 5/91. Accepted 12/17/91.

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