Array CGH Analysis for PTCL-U Revealed a Distinct Subgroup with Pathological and Clinical Relevance.

Peripheral T-cell lymphoma, unspecified (PTCL-U) is one of the most commonly encountered group among peripheral T-cell lymphomas (PTCLs). This category consists of the cases which do not belong to any of the recognized subtypes of PTCLs in the World Health Organization classification. PTCL-U comprises histologically and clinically heterogeneous groups, which makes it difficult to assess conventional therapies accurately and to develop new therapeutic targets. The first priority is thus to identify subgroups of PTCL-U. However, the molecular basis of their clinical heterogeneity is still poorly understood. Here we analyzed 51 cases of PTCL-U by means of array CGH consisting of 2304 artificial chromosome clones that cover the whole genome at a 1.3 mega base resolution. DNA gains and losses were detected in 29 cases (total regions: average 15.6, range 1–31; gains: average 8.0 regions, range 0–24; losses: average 7.6 regions, range 0–21). Regions of frequent gain(>15%; ≥5cases) were detected on 1q24.2, 1q25.1–25.2, 3q25–26.1, 3q26.2–27.1, 3q27.3–29, 4p16.2–15.2, 4q21.1–21.21, 4q21.23–28.1, 4q28.3–31.23, 4q32.1, 4q32.3–35.1, 7p, 7q, 9q31.3–32, 9q33.2–34.2, 11q14.1, 11q14.3-tel, and 16p13.2–12.2, and regions of frequent loss on 1p31.2–13.1, 2q37.3, 6q14.3, 9p21.3, 10p14–13, 10p12.31–11.22, 10q11.21–21.1, 10q23.2–23.31, 10q24.2–26.3, 13q14.11–14.2, 13q21.1–34, 16q12.1–21, 17p13.3–11.2, and 18p11.31d–11.22b. Three consecutive BAC clones at 14q32.2 and at 9p21.3 were identified as regions of recurrent high-level amplification and homozygous loss, respectively. Our array CGH analysis could reveal a distinct subgroup consisted of 29 cases which have genomic alterations. Regarding to tumor burden, histopathology, the expression of chemokine receptors, and prognosis, this subgroup displayed significantly different features compared with 22 cases showing no genomic alteration. Our findings showed that PTCL-U with genomic alteration has pathological and clinical relevance distinct from those without, implying that distinct mechanisms underlay in molecular pathogenesis of PTCL-U.