Immunoglobulin Gene Transcripts Have Distinct V(H)DJ(H) Recombination Characteristics in Human Epithelial Cancer Cells

It was well accepted that only B-lymphocytes and plasma cells expressed immunoglobulin (Ig) gene. However, our group and others have confirmed that non-B-cells, such as epithelial cancer cells, can also express Ig. The aim of this work is to elucidate the role of non-B-cell-derived Ig by investigating the characteristics of the Ig heavy chain (IgH) gene repertoire in epithelial cancer cells. We cloned and sequenced 89 V(H)DJ(H) (V-D-J recombination of the IgH variable region) transcripts by microdissecting cells from eight different types of epithelial cancers and two cancer cell lines (HT-29 and HeLa S3). The cancer-derived Ig gene repertoire showed specific restricted patterns of V(H)DJ(H) recombination with seven sets of predominant V(H)DJ(H) sequences. Surprisingly, within a set of V(H)DJ(H) recombination, the variable (V) sequences derived from different cancer types had not only identical heavy chain variable (V-H), diversity (D), and joining (JH) segments usage, but also identical junctions and mutation targets in the V-H region. The V(H gamma)DJ(H gamma) (but not V(H mu)DJ(H mu)) in the cancer-derived sequences had a high mutation rate; however, it was shown that the mechanism of hypermutation was different from antigen selection in B-cell-derived V(H gamma)DJ(H gamma) sequences. In contrast to V(H mu)DJ(H mu), the V(H gamma)DJ(H gamma) sequences did not appear to originate from classical class switching. These results suggest that cancer-derived Ig genes have a distinct repertoire that may have implications for their role in carcinogenesis.Biochemistry & Molecular BiologySCI(E)EIPubMed23ARTICLE2013610-1361928