Abstract
Abstract 298
Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a heterogeneous group of nodal and extra-nodal mature T-cell lymphomas that do not belong to any of the hitherto characterized T cell lymphoma subtypes. Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). PTCL, NOS with genomic aberrations has been shown to resemble lymphoma-type ATLL in terms of genomic aberration patterns, histopathology and prognosis (Clin Cancer Res., 15:30–38). We have recently shown that a majority of patients with acute-type ATLL have multiple subclones that were likely produced in lymph nodes (Blood, 117:5473–5478). In this study, high-resolution oligo-array comparative genomic hybridization (CGH) was employed to determine whether PTCL, NOS with genomic aberrations also possesses multiple subclones as found in ATLL. Thirteen cases of PTCL, NOS were available for 44K high-resolution array CGH analysis. These samples analyzed in this study were shown to be monoclonal by Southern blot analysis. We obtained average log2 ratios of regions where aberrations continued over 400 probes and showed a linear average ratio of >0.1 or <-0.1. The log2 ratio imbalance was defined when a patient had a different average log2 ratio for gain or loss regions. The results showed that 11 of the 13 cases (84.6%) had a log2 ratio imbalance, suggesting that multiple subclones exist in PTCL, NOS with genomic aberrations. As previously demonstrated, the average log2 ratio of aberrant regions reflected the ratio of tumors (Blood, 117:5473–5478). In one case, as represented in Figure 1, all tumor cells had regions of loss on chromosomes 3 and 13. Fifty-four percent of tumor cells had a region of loss on chromosome 16, and 83% of tumor cells had loss on chromosome 17. It is therefore speculated that clonal evolution took place as shown in Figure 2. In an effort to examine the association between multiple subclones and prognosis, we used our previous BAC array data for 24 cases and found that the presence of multiple subclones was associated with a poor prognosis (p=0.0279) (Figure 3). Our finding concerning the presence of multiple subclones in PTCL, NOS and ATLL should assist greatly in revealing the mechanism of lymphoma development, progression and drug-resistance associated with these diseases.
No relevant conflicts of interest to declare.
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