Immunoglobulin gene transcripts have distinct VHDJH 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 (VH), diversity (D), and joining (JH) segments usage, but also identical junctions and mutation targets in the V(H) region. The V(Hgamma)DJ(Hgamma) (but not V(Hmicro)DJ(Hmicro)) 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(Hgamma)DJ(Hgamma)sequences. In contrast to V(Hmicro)DJ(Hmicro), the V(Hgamma)DJ(Hgamma) 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.
Zheng
Jie
J
Peking University Center for Human Disease Genomics, Beijing, 100191, China.
Huang
Jing
J
Peking University Center for Human Disease Genomics, Beijing, 100191, China.
Mao
Yuntao
Y
Peking University Center for Human Disease Genomics, Beijing, 100191, China.
Liu
Shiqing
S
Peking University Center for Human Disease Genomics, Beijing, 100191, China.
Sun
Xin
X
Peking University Center for Human Disease Genomics, Beijing, 100191, China.
Zhu
Xiaohui
X
Peking University Center for Human Disease Genomics, Beijing, 100191, China.
Ma
Teng
T
Peking University Center for Human Disease Genomics, Beijing, 100191, China.
Zhang
Li
L
Peking University Center for Human Disease Genomics, Beijing, 100191, China.
Ji
Jiafu
J
Department of Surgery, Peking University School of Oncology, Beijing, 100142, China.
Zhang
Youhui
Y
Department of Immunology, Cancer Institute, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100021, China.
Yin
C Cameron
CC
Department of Hematopathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.
Qiu
Xiaoyan
X
Peking University Center for Human Disease Genomics, Beijing, 100191, China. Electronic address: qiuxy@bjmu.edu.cn.
D006367:HeLa Cells; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism*; D027041:Somatic Hypermutation, Immunoglobulin
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009363:Neoplasm Proteins