Array CGH Analysis for PTCL-U Revealed Two Genetically Distinct Subgroups.

Peripheral T-cell lymphoma, unspecified (PTCL-U) is the most common group among Peripheral T-cell lymphomas (PTCLs). This category consists of the cases which do not belong to any of the recognizable subtypes of PTCLs in WHO classification. PTCL-U comprises heterogeneous groups in morphology and phenotype. Molecular basis of clinical heterogeneity is needed to identify distinct subgroups with clnical relevance. Several reports of conventional cytogenetic studies including comparative genomic hybridization (CGH) showed some recurrent aberrations, but failed to identify the genetic hallmarks to categorize distinct subgroups. So far, no array-based comparative genomic hybridization (array CGH) study for PTCL-U has been reported. Here we analyzed 29 cases of PTCL-U by means of array CGH consisting of 2265 artificial chromosome clones that cover the whole genome at a 1.3 mega base resolution. The analysis clearly divided these cases into two distinct subgroups on the basis of frequency of genomic alterations. One group consists of 17 cases which showed significant lower copy number changes (average copy number gains: 0.5 regions, average copy number losses: 0.1 regions). The other group had average copy number gains of 15.7 regions and losses of 15.0 regions in 12 cases. We designate the former as “simple type” and the latter as “complex type”. In the complex type, regions of recurrent (>20%) gain are detected on chromosome 1q23.3-24.2, 3q25.31-tel, 4p15.1-16.1, 4q28.3-31.23, 5q34, 6p24.1-25.1, 7p21.3-tel, 7p21.1, 7q, 8q24.23, 11q13.4-tel, 12p11.21-11.22, 16p12.3-13.3, 17q11.2-22. Regions of recurrent (>20%) losses are detected on chromosome 1p13.1-13.3, 2q37.3, 4q21.21-21.23, 4q34.3-35.1, 5q21.2-23.1, 6p12.1-q14.3, 6q23.2-24.1, 6q25.1-26, 7p14.3-22.1, 9p21.3, 10p14-qtel, 12p13.1-13.2, 13, 14q12, 16q, 17p, 18p, 20q13-2, 22q11.21-12.2. Median age is 62 years in the simple type and 73 years in the complex type, respectively. Median survival is 27 months in the simple type and 11 months in the complex type. Log-rank test for overall survival between the simple type and the complex type showed inferior survival for the complex type but significance was marginal (p=0.21). Our findings showed that PTCL-U comprised two genetically distinct subgroups, implying that distinct mechanisms underlay in molecular pathogenesis of PTCL-U. Furthermore cilinicopathological features of each group are also being studied.