Tan Kar-Tong, Ding Ling-Wen, Sun Qiao-Yang, Lao Zhen-Tang, Chien Wenwen, Ren Xi, Xiao Jin-Fen, Loh Xin Yi, Xu Liang, Lill Michael, Mayakonda Anand, Lin De-Chen, Yang Henry, Koeffler H Phillip
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Department of Haematology, Singapore General Hospital, Singapore, Singapore.
BMC Cancer. 2018 Oct 1;18(1):940. doi: 10.1186/s12885-018-4840-5.
Clonal VDJ rearrangement of B/T cell receptors (B/TCRs) occurring during B/T lymphocyte development has been used as a marker to track the clonality of B/T cell populations.
We systematically profiled the B/T cell receptor repertoire of 936 cancer cell lines across a variety of cancer types as well as 462 Epstein-Barr Virus (EBV) transformed normal B lymphocyte lines using RNA sequencing data.
Rearranged B/TCRs were readily detected in cell lines derived from lymphocytes, and subclonality or potential biclonality were found in a number of blood cancer cell lines. Clonal BCR/TCR rearrangements were detected in several blast phase CML lines and unexpectedly, one gastric cancer cell line (KE-97), reflecting a lymphoid origin of these cells. Notably, clonality was highly prevalent in EBV transformed B lymphocytes, suggesting either transformation only occurred in a few B cells or those with a growth advantage dominated the transformed population through clonal evolution.
Our analysis reveals the complexity and heterogeneity of the BCR/TCR rearrangement repertoire and provides a unique insight into the clonality of lymphocyte derived cell lines.
B/T淋巴细胞发育过程中发生的B/T细胞受体(B/TCRs)的克隆性VDJ重排已被用作追踪B/T细胞群体克隆性的标志物。
我们利用RNA测序数据系统地分析了936种不同癌症类型的癌细胞系以及462种爱泼斯坦-巴尔病毒(EBV)转化的正常B淋巴细胞系的B/T细胞受体库。
在来源于淋巴细胞的细胞系中很容易检测到重排的B/TCRs,并且在一些血液癌细胞系中发现了亚克隆性或潜在的双克隆性。在几个急变期慢性粒细胞白血病细胞系中检测到了克隆性BCR/TCR重排,出乎意料的是,在一个胃癌细胞系(KE-97)中也检测到了,这反映了这些细胞的淋巴样起源。值得注意的是,克隆性在EBV转化的B淋巴细胞中非常普遍,这表明要么转化仅发生在少数B细胞中,要么具有生长优势的细胞通过克隆进化在转化群体中占主导地位。
我们的分析揭示了BCR/TCR重排库的复杂性和异质性,并为淋巴细胞来源的细胞系的克隆性提供了独特的见解。