Identification of subtype-specific genomic alterations in adult T-cell leukemia/lymphoma

侵袭性成人T细胞白血病/淋巴瘤（ATLL），如急性和淋巴瘤型，是预后不良的致命性疾病。虽然这两种亚型具有不同的临床病理学特征，但尚未报道基因组/遗传改变的详细比较分析。我们对17例急性和49例淋巴瘤病例进行了基于阵列的比较基因组杂交以及实时定量PCR，以确定复发扩增区域的靶基因。比较急性型和淋巴瘤型的基因组图谱显示，淋巴瘤型在1 q、2 p、4 q、7 p和7 q处有显著更频繁的增加，而在10 p、13 q、16 q和18 p处有显著更频繁的丢失，而急性型显示3/3 p的增加。在淋巴瘤型中发现的1 p36、6p 25、7 p22、7 q和14 q32处的反复高水平扩增中，我们能够证明CARMA I是淋巴瘤型而不是急性型的7 p22扩增的可能靶基因。此外，我们发现BCL 11B在急性型中过度表达，而在淋巴瘤型中没有或低表达，而与14 q32获得/扩增无关。这些结果表明，急性和淋巴瘤类型是基因组不同的亚型，因此可能通过不同的基因型发生肿瘤。

Aggressive adult T-cell leukemia/lymphoma (ATLL) such as acute and lymphoma types are fatal diseases with poor prognosis. Although these two subtypes feature different clinicopathological characteristics, no detailed comparative analyses of genomic/genetic alterations have been reported. We performed array-based comparative genomic hybridization for 17 acute and 49 lymphoma cases as well as real-time quantitative PCR to identify the target genes of recurrently amplified regions. Comparison of the genome profiles of acute and lymphoma types revealed that the lymphoma type had significantly more frequent gains at 1q, 2p, 4q, 7p and 7q, and losses of 10p, 13q, 16q and 18p, whereas the acute type showed a gain of 3/3p. Of the recurrent high-level amplifications found at 1p36, 6p25, 7p22, 7q and 14q32 in the lymphoma type, we were able to demonstrate that CARMA I is a possible target gene of the 7p22 amplification for the lymphoma type but not for the acute type. Furthermore, we found BCL11B overexpression in acute type irrespective of the 14q32 gain/amplification, while no or low expression of the gene in the lymphoma type. These results suggest that acute and lymphoma types are genomically distinct subtypes, and thus may develop tumors via disti