Thurston V C, Ceperich T M, Vance G H, Heerema N A
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202, USA.
Cancer Genet Cytogenet. 1999 Mar;109(2):154-60. doi: 10.1016/s0165-4608(98)00167-8.
Monosomy 7 is frequently found in the bone marrow of patients with Fanconi anemia (FA), marrow myelodysplasia, or acute myelogenous leukemia and is associated with poor prognosis. In our laboratory, cytogenetic analysis of bone marrow from an FA patient found 2 of 30 cells with monosomy 7, but the results of fluorescence in situ hybridization (FISH) indicated that 83 of 207 cells (40%) had monosomy 7. FISH was then used to analyze two earlier samples from the index case, neither of which had monosomy 7 as determined by standard cytogenetics. The FISH analysis determined that the first sample, taken 19 months earlier, had 8 of 200 cells (4%) with monosomy 7 and the second sample. taken 7 months later, contained 43 of 200 cells (21.5%) with monosomy 7. These results indicate a slow evolution toward monosomy 7 in the patient's bone marrow. Standard metaphase chromosome analysis represents only spontaneously dividing cells, leading us to hypothesize that FISH was detecting monosomy 7 in nondividing cells and that it might be useful in the early detection of abnormal clones. To test this hypothesis, FISH was performed on 13 bone marrow samples from nine patients with FA who did not exhibit monosomy 7 by cytogenetic analysis. Monosomy 7 was detected in 3.44% of nuclei in FA patients and in 3% of nuclei in normal controls. To date, none of these nine FA patients have developed monosomy 7 or leukemia. They are being monitored by standard cytogenetics and by FISH to determine whether monosomy 7 develops and whether it can be detected by FISH prior to its detection by standard cytogenetics. As standard practice, we have adopted FISH analysis for monosomy 7 in all patients with FA.
7号染色体单体常见于范可尼贫血（FA）、骨髓增生异常或急性髓性白血病患者的骨髓中，且与预后不良相关。在我们实验室，对一名FA患者的骨髓进行细胞遗传学分析时，在30个细胞中发现2个有7号染色体单体，但荧光原位杂交（FISH）结果显示，207个细胞中有83个（40%）存在7号染色体单体。随后，FISH被用于分析该索引病例的两份更早的样本，通过标准细胞遗传学检测，这两份样本均未发现7号染色体单体。FISH分析确定，19个月前采集的第一份样本中，200个细胞里有8个（4%）存在7号染色体单体；7个月后采集的第二份样本中，200个细胞里有43个（21.5%）存在7号染色体单体。这些结果表明，该患者骨髓中向7号染色体单体的演变较为缓慢。标准中期染色体分析仅代表自发分裂的细胞，这使我们推测，FISH检测到的是不分裂细胞中的7号染色体单体，并且它可能有助于早期检测异常克隆。为验证这一假设，对9名经细胞遗传学分析未表现出7号染色体单体的FA患者的13份骨髓样本进行了FISH检测。在FA患者中，3.44%的细胞核检测到7号染色体单体，正常对照中这一比例为3%。截至目前，这9名FA患者均未出现7号染色体单体或白血病。他们正通过标准细胞遗传学和FISH进行监测，以确定是否会出现7号染色体单体，以及在标准细胞遗传学检测到之前FISH能否检测到。作为标准操作，我们已对所有FA患者采用FISH分析检测7号染色体单体。
