Abe Akihiro, Katsumi Akira, Kobayashi Miki, Okamoto Akinao, Tokuda Masutaka, Kanie Tadaharu, Yamamoto Yukiya, Naoe Tomoki, Emi Nobuhiko
Department of Hematology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Cancer Genet. 2012 Nov;205(11):608-11. doi: 10.1016/j.cancergen.2012.10.001. Epub 2012 Oct 24.
The RUNX1 locus, which encodes a transcription factor that is essential for normal hematopoiesis, is a frequent location of chromosomal rearrangements in human hematological malignancies. We report the case of a 78-year-old man with acute myeloid leukemia (AML), M1 subtype (French-American-British classification), with a t(11;21)(p14;q22). Fluorescence in situ hybridization showed a split signal for RUNX1, which indicated that RUNX1 was involved in this translocation. Using 3'-rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction analyses, we found that RUNX1 was fused to C11orf41 on 11p14 and detected two in-frame C11orf41-RUNX1 fusion transcripts. One was a fusion between exon 5 of RUNX1 and exon 13 of C11orf41, and the other was between exon 6 of RUNX1 and exon 13 of C11orf41. This suggested that the RUNX1 breakpoint was in intron 6 and had generated alternative fusion splice variants. A reciprocal C11orf41-RUNX1 fusion was not detected. Thus, we identified C11orf41 as a novel fusion partner of RUNX1 in AML.
RUNX1基因座编码一种对正常造血至关重要的转录因子，是人类血液系统恶性肿瘤中染色体重排的常见位点。我们报告了一例78岁男性急性髓系白血病（AML）患者，M1亚型（法美英分类法），伴有t(11;21)(p14;q22)。荧光原位杂交显示RUNX1出现分裂信号，表明RUNX1参与了此次易位。通过3'-cDNA末端快速扩增和逆转录-聚合酶链反应分析，我们发现RUNX1与11p14上的C11orf41融合，并检测到两种读码框内的C11orf41-RUNX1融合转录本。一种是RUNX1的外显子5与C11orf41的外显子13融合，另一种是RUNX1的外显子6与C11orf41的外显子13融合。这表明RUNX1的断点位于内含子6，并产生了替代的融合剪接变体。未检测到相互的C11orf41-RUNX1融合。因此，我们在AML中鉴定出C11orf41是RUNX1的一种新型融合伴侣。
