Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
Department of Haematology, Oslo University Hospital, Oslo, Norway.
Cancer Genomics Proteomics. 2019 May-Jun;16(3):175-178. doi: 10.21873/cgp.20123.
BACKGROUND/AIM: The aim of the study was to determine the genetic and molecular consequences of trisomy 4, a recurrent but rare chromosomal abnormality in acute myeloid leukemia (AML).
Interphase fluorescence in situ hybridization, reverse transcriptase-quantitative polymerase chain reaction for 28 chromosomal gene translocations/fusion genes, and targeted sequencing analyses were performed on five AMLs with trisomy 4 as the sole chromosomal anomaly.
An NPM1 frameshift mutation was found in all leukemic bone marrows, DNMT3A, FLT3, and IDH1 mutations were found in three, KIT and NRAS mutations in two, whereas IDH2 (R140Q), RUNX1, and WT1 mutations were found in only one patient each. The three patients with a DNMT3A (R882H) mutation have died. In contrast, the two patients whose leukemic cells were without this mutation, are alive 55 and 31 months after diagnosis, respectively.
The results suggest a possible association between trisomy 4 and additional mutations that may influence prognosis.
背景/目的：本研究旨在确定 4 号染色体三体，这是急性髓细胞白血病（AML）中一种常见但罕见的染色体异常，所导致的遗传和分子后果。
对五例仅存在 4 号染色体三体这一染色体异常的 AML 进行间期荧光原位杂交、28 种染色体基因易位/融合基因的逆转录定量聚合酶链反应和靶向测序分析。
所有白血病骨髓中均发现 NPM1 移码突变，3 例存在 DNMT3A、FLT3 和 IDH1 突变，2 例存在 KIT 和 NRAS 突变，而仅 1 例各存在 IDH2（R140Q）、RUNX1 和 WT1 突变。3 例存在 DNMT3A（R882H）突变的患者已死亡。相比之下，白血病细胞中不存在该突变的 2 例患者，分别在诊断后 55 个月和 31 个月时仍存活。
这些结果表明，4 号染色体三体与可能影响预后的其他突变之间可能存在关联。
