Center for Individualized Medicine-Biomarker Discovery, Mayo Clinic, Rochester, MN, USA.
Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Blood Cancer J. 2019 Dec 16;9(12):103. doi: 10.1038/s41408-019-0255-z.
Fluorescence in situ hybridization (FISH) is currently the gold-standard assay to detect recurrent genomic abnormalities of prognostic significance in multiple myeloma (MM). Since most translocations in MM involve a position effect with heterogeneous breakpoints, we hypothesize that FISH has the potential to miss translocations involving these regions. We evaluated 70 bone marrow samples from patients with plasma cell dyscrasia by FISH and whole-genome mate-pair sequencing (MPseq). Thirty cases (42.9%) displayed at least one instance of discordance between FISH and MPseq for each primary and secondary abnormality evaluated. Nine cases had abnormalities detected by FISH that went undetected by MPseq including 6 tetraploid clones and three cases with missed copy number abnormalities. In contrast, 19 cases had abnormalities detected by MPseq that went undetected by FISH. Seventeen were MYC rearrangements and two were 17p deletions. MPseq identified 36 MYC abnormalities and 17 (50.0% of MYC abnormal group with FISH results) displayed a false negative FISH result. MPseq identified 10 cases (14.3%) with IgL rearrangements, a recent marker of poor outcome, and 10% with abnormalities in genes associated with lenalidomide response or resistance. In summary, MPseq was superior in the characterization of rearrangement complexity and identification of secondary abnormalities demonstrating increased clinical value compared to FISH.
荧光原位杂交（FISH）是目前检测多发性骨髓瘤（MM）中具有预后意义的复发性基因组异常的金标准检测方法。由于 MM 中的大多数易位涉及具有异质性断裂点的位置效应，我们假设 FISH 有可能会错过涉及这些区域的易位。我们通过 FISH 和全基因组配对测序（MPseq）评估了 70 例浆细胞发育异常患者的 70 例骨髓样本。在所评估的每个原发性和继发性异常中，有 30 例（42.9％）显示 FISH 和 MPseq 之间至少存在一次不一致。FISH 检测到 9 例异常，但 MPseq 未检测到，包括 6 个四倍体克隆和 3 例未检测到的拷贝数异常。相比之下，MPseq 检测到 19 例 FISH 未检测到的异常。其中 17 例为 MYC 易位，2 例为 17p 缺失。MPseq 鉴定出 36 例 MYC 异常，其中 17 例（FISH 结果异常的 MYC 异常组的 50.0％）显示出假阴性 FISH 结果。MPseq 鉴定出 10 例（14.3％）具有 IgL 重排，这是预后不良的新标志物，10％具有与 lenalidomide 反应或耐药性相关的基因异常。总之，与 FISH 相比，MPseq 在易位复杂性的表征和继发性异常的识别方面具有优势，显示出更高的临床价值。
