Deeb George, Baer Maria R, Gaile Daniel P, Sait Sheila N Jani, Barcos Maurice, Wetzler Meir, Conroy Jeffrey M, Nowak Norma J, Cowell John K, Cheney Richard T
Department of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Genes Chromosomes Cancer. 2005 Dec;44(4):373-83. doi: 10.1002/gcc.20239.
Myeloid sarcoma (MS) is a tumor mass of myeloblasts or immature myeloid cells occurring in an extramedullary site. In this study, seven cases of MS [stomach (1), testis (1), skin (2), and lymph node (3)] and 3 synchronous and 1 follow-up bone marrow (BM) samples were studied for genomic abnormalities using array comparative genomic hybridization (array-CGH). Array-CGH construction used approximately 5,400 bacterial artificial chromosome clones from the RPCI-11 library, spanning the human genome. Data were analyzed using the DNAcopy software and custom heuristics. All MS cases had genomic abnormalities detected by array-CGH. Unbalanced genomic abnormalities in five MS cases were confirmed by conventional cytogenetics (CC) and/or fluorescence in situ hybridization (FISH); these abnormalities included loss of 4q32.1-q35.2, 6q16.1-q21, and 12p12.2-p13.2 and gain of 8q21.2-q24.3, 8, 11q21-q25, 13q21.32-q34, 19, and 21. Array-CGH was also invaluable in identifying possible deletions, partner translocations, and breakpoints that were questionable by CC. The remaining two MS cases had genomic aberrations detected by array-CGH, but were not studied further by CC/FISH. Chromosome 8 was most commonly abnormal (3/7 cases). Identical genomic abnormalities were demonstrated in MS and in synchronous BM in two cases. These results demonstrate that array-CGH is a powerful tool to screen MS tissue for unbalanced genomic abnormalities, allowing identification of chromosome abnormalities when concurrent BM is nonanalyzable or nonleukemic.
髓系肉瘤(MS)是一种发生于髓外部位的成髓细胞或未成熟髓系细胞的肿瘤团块。在本研究中,我们使用阵列比较基因组杂交技术(array-CGH)对7例MS患者[胃(1例)、睾丸(1例)、皮肤(2例)和淋巴结(3例)]以及3例同步和1例随访的骨髓(BM)样本进行了基因组异常研究。Array-CGH构建使用了来自RPCI-11文库的约5400个细菌人工染色体克隆,覆盖人类基因组。使用DNAcopy软件和定制启发式算法对数据进行分析。所有MS病例均通过array-CGH检测到基因组异常。5例MS病例中的基因组不平衡异常通过传统细胞遗传学(CC)和/或荧光原位杂交(FISH)得到证实;这些异常包括4q32.1-q35.2、6q16.1-q21和12p12.2-p13.2缺失以及8q21.2-q24.3、8、11q21-q25、13q21.32-q34、19和21增益。Array-CGH在识别CC难以确定的可能缺失、伙伴易位和断点方面也具有重要价值。其余2例MS病例通过array-CGH检测到基因组畸变,但未进一步进行CC/FISH研究。8号染色体最常出现异常(7例中有3例)。2例MS患者及其同步BM中出现了相同的基因组异常。这些结果表明,array-CGH是一种筛查MS组织基因组不平衡异常的有力工具,当同时存在的BM无法分析或无白血病时,可用于识别染色体异常。