Liu J, Nau M M, Zucman-Rossi J, Powell J I, Allegra C J, Wright J J
NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.
Genes Chromosomes Cancer. 1997 Mar;18(3):232-9. doi: 10.1002/(sici)1098-2264(199703)18:3<232::aid-gcc10>3.0.co;2-k.
A t(11;22)(p13;p12) chromosomal translocation, juxtaposing the Wilms' tumor (WT1) and Ewing's sarcoma (EWS) genes, is the cytogenetic hallmark of desmoplastic small round cell tumor (DSRCT), a primitive multiphenotypic sarcoma arising in serosal tissues. Chimeric transcripts generated by this rearrangement encode an aberrant transcription factor that fuses the 5' region of EWS with a 3' WT1 segment. We describe the insertion of a LINE-I DNA mobile genetic element at the genomic breakpoint of a DSRCT chromosomal translocation. A 480 bp heterologous DNA segment with homology to the LINE-I DNA consensus sequence was located between EWS intron 8 and WT1 exon 8 in the productively rearranged allele. Sequence homology corresponded to the LINE-I ORF-2, which encodes a protein with reverse-transcriptase activity. The heterologous inserted fragment was not evident in the germline of normal tissue from the patient, suggesting that transposition occurred in somatic cells, possibly during the process of chromosomal rearrangement. This case represents the first example of LINE-I DNA transposition at the fusion site of a tumor-associated chromosomal rearrangement.
t(11;22)(p13;p12)染色体易位，使威尔姆斯瘤（WT1）基因与尤因肉瘤（EWS）基因并列，是促纤维组织增生性小圆细胞瘤（DSRCT）的细胞遗传学特征，DSRCT是一种起源于浆膜组织的原始多表型肉瘤。这种重排产生的嵌合转录本编码一种异常转录因子，该因子将EWS的5'区域与WT1的3'片段融合。我们描述了一个LINE-1 DNA可移动遗传元件插入到DSRCT染色体易位的基因组断点处。在有效重排的等位基因中，一个与LINE-1 DNA共有序列具有同源性的480 bp异源DNA片段位于EWS内含子8和WT1外显子8之间。序列同源性对应于LINE-1 ORF-2，它编码一种具有逆转录酶活性的蛋白质。在患者正常组织的种系中未发现异源插入片段，这表明转座发生在体细胞中，可能是在染色体重排过程中。该病例代表了LINE-1 DNA在肿瘤相关染色体重排融合位点转座的首个实例。
