Karhu R, Siitonen S, Tanner M, Keinänen M, Mäkipernaa A, Lehtinen M, Vilpo J A, Isola J
Laboratory of Cancer Genetics, Tampere University Hospital, Finland.
Cancer Genet Cytogenet. 1997 Jun;95(2):123-9. doi: 10.1016/s0165-4608(96)00242-7.
Classical cytogenetic analysis plays an important role in the diagnosis and classification of childhood acute lymphoblastic leukemia (ALL). However, poor in vitro growth of the malignant cells and suboptimal quality of metaphase spreads may sometimes cause false-negative findings (normal karyotype). We used comparative genomic hybridization (CGH) to study whether this new method is able to detect and characterize genetic aberrations not detected by karyotyping. CGH showed clonal genetic aberrations in 8 of 13 cases, most of which showed gains of several chromosomes, indicating hyperdiploidy. The sensitivity of CGH was sufficient to detect a small interstitial deletion of 6q. One karyotypically complex case was resolved by CGH showing a high-level amplification of DNA sequences originating from the 12p12-13. Interphase fluorescence in situ hybridization (FISH) analyses confirmed the CGH findings in 2 cases, validating the accuracy of CGH. In conclusion, CGH experiments established the known fact that hyperdiploidy is the most common finding in pediatric ALLs and that CGH may detect aberrations that are not seen in the G-banded karyotype. CGH was also able to further characterize genetic aberrations such as gene amplification, which is occasionally involved in pediatric ALL as well as in other leukemias.
经典细胞遗传学分析在儿童急性淋巴细胞白血病（ALL）的诊断和分类中起着重要作用。然而，恶性细胞体外生长不佳以及中期分裂相铺片质量欠佳有时可能导致假阴性结果（核型正常）。我们使用比较基因组杂交（CGH）来研究这种新方法是否能够检测和鉴定核型分析未检测到的基因畸变。CGH显示13例中有8例存在克隆性基因畸变，其中大多数显示多条染色体增加，提示超二倍体。CGH的灵敏度足以检测到6q的小间隙缺失。通过CGH解析了1例核型复杂的病例，显示源自12p12 - 13的DNA序列高水平扩增。间期荧光原位杂交（FISH）分析在2例中证实了CGH结果，验证了CGH的准确性。总之，CGH实验证实了超二倍体是儿童ALL中最常见的发现这一已知事实，并且CGH可能检测到G带核型中未见的畸变。CGH还能够进一步鉴定基因扩增等基因畸变，基因扩增偶尔也见于儿童ALL以及其他白血病。
