Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, Universitá degli Studi di Milano, Milan, Italy.
Department of Dermatology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy.
Genes Chromosomes Cancer. 2018 Dec;57(12):622-629. doi: 10.1002/gcc.22673. Epub 2018 Oct 11.
Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (pcAECyTCL) is a rare provisionally categorized cutaneous lymphoma characterized by an aggressive course. Its pathogenesis and molecular mechanisms are still unknown, and only two individual cases have so far been molecularly characterized. The aim of this study was to define the pattern of numerical chromosomal alterations in tumor samples taken from 20 patients with pcAECyTCL at the time of diagnosis by means of array-comparative genomic hybridization (a-CGH). a-CGH detected numerous genomic aberrations in all the patients and, putting these together as a whole, they affected all the chromosomes. However, no specific profile of recurrent copy number alterations (CNAs) was found. Most of the gains involved regions previously described in other aggressive cutaneous lymphomas such as 7q, 8q24.3, and 17q, whereas the most significant CNA was the loss of 9p21.3 (CDKN2A-CDKN2B), which has already been found in a variety of malignant tumors and is associated with aggressive cutaneous T-cell lymphomas. In brief, CGH analysis revealed a large number of CNAs with only few recurring regions that probably do not represent driving events. The genomic instability found in this aggressive variant of cutaneous lymphoma may therefore be a secondary event but, at the time of the diagnosis of pcAECyTCL, the genomic integrity of tumor cells is already compromised.
原发性皮肤 CD8+侵袭性表皮亲表皮细胞毒性 T 细胞淋巴瘤(pcAECyTCL)是一种罕见的暂定分类皮肤淋巴瘤,具有侵袭性病程。其发病机制和分子机制尚不清楚,迄今为止只有两例个体病例进行了分子特征分析。本研究旨在通过 array-comparative genomic hybridization(a-CGH)在诊断时对 20 例 pcAECyTCL 患者的肿瘤样本中定义数值染色体改变的模式。a-CGH 在所有患者中检测到大量基因组异常,将这些异常综合在一起,它们影响了所有染色体。然而,没有发现特定的重现性拷贝数改变(CNA)模式。大多数增益涉及到先前在其他侵袭性皮肤淋巴瘤中描述的区域,如 7q、8q24.3 和 17q,而最显著的 CNA 是 9p21.3(CDKN2A-CDKN2B)的缺失,该缺失已在多种恶性肿瘤中发现,与侵袭性皮肤 T 细胞淋巴瘤有关。简而言之,CGH 分析显示了大量的 CNA,只有少数重现区域,这些区域可能不是驱动事件。因此,在这种侵袭性皮肤淋巴瘤变体中发现的基因组不稳定性可能是继发事件,但在诊断 pcAECyTCL 时,肿瘤细胞的基因组完整性已经受到损害。