Dept. of Pathology and Laboratory Medicine, University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104-4283, USA.
Am J Clin Pathol. 2011 Jun;135(6):921-8. doi: 10.1309/AJCPJCW6BY0CNIHD.
In this study, we correlated the results of concurrent molecular and cytogenetic detection of entity-defining translocations in adults with acute leukemia to determine the frequency of cryptic translocations missed by conventional cytogenetics (CC) and of recurrent, prognostically relevant translocations not detectable by multiplex reverse transcriptase-polymerase chain reaction (MRP). During a 5.5-year period, 442 diagnostic acute leukemia specimens were submitted for MRP-based detection of 7 common recurrent translocations: t(8;21), t(15;17), inv(16), t(9;22), t(12;21), t(4;11), and t(1;19), with a detection rate of 15.2% (67/442). CC was performed in 330 (74.7%) of 442 cases. In 7 of these 330 cases, CC missed the translocation detected by MRP. In 50 additional cases, CC revealed 1 of the MRP-detectable translocations (all were also MRP positive), yielding a false-negative rate of 12% (7/57) for the CC assay. The remaining 140 of 190 cases with clonal cytogenetic changes harbored abnormalities that were not targeted by the MRP assay, including 8 that define specific acute myeloid leukemia entities. This study revealed the frequent occurrence of false-negative, entity-defining CC analysis and highlighted the complementary nature of MRP and CC approaches in detecting genetic abnormalities in acute leukemia.
在这项研究中，我们将成人急性白血病实体定义性易位的同时进行分子和细胞遗传学检测的结果进行相关分析，以确定常规细胞遗传学（CC）漏诊的隐匿性易位的频率，以及不能通过多重反转录-聚合酶链反应（MRP）检测到的复发性、具有预后意义的易位的频率。在 5.5 年期间，442 份诊断性急性白血病标本提交进行基于 MRP 的 7 种常见复发性易位检测：t(8;21)、t(15;17)、inv(16)、t(9;22)、t(12;21)、t(4;11)和 t(1;19)，检测率为 15.2%（67/442）。在 442 例中的 330 例（74.7%）中进行了 CC。在这 330 例中的 7 例中，CC 漏诊了 MRP 检测到的易位。在另外 50 例中，CC 显示了 1 种 MRP 可检测的易位（均为 MRP 阳性），CC 检测的假阴性率为 12%（7/57）。在 190 例具有克隆细胞遗传学改变的病例中，其余 140 例未被 MRP 检测到，包括 8 例定义了特定的急性髓系白血病实体。这项研究揭示了 CC 分析中频繁出现的假阴性、实体定义性异常，突出了 MRP 和 CC 方法在检测急性白血病遗传异常方面的互补性。
