Hejlik D P, Kottickal L V, Liang H, Fairman J, Davis T, Janecki T, Sexton D, Perry W, Tavtigian S V, Teng D H, Nagarajan L
Section of Molecular Hematology and Therapy, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer Res. 1997 Sep 1;57(17):3779-83.
Acquired interstitial or complete losses of chromosome 5 are recurring anomalies associated with preleukemic myelodysplasia and acute myelogenous leukemia with a poor prognosis. Previous studies have delineated a potential myeloid tumor suppressor locus to a <2.4-Mb interval between the genes for IL9 and EGR1 on 5q31. In this report, we have localized the SMAD5 gene, a homologue of the tumor suppressor genes SMAD4/DPC-4 and SMAD2/JV18.1, to the minimal myeloid tumor suppressor locus and characterized its open reading frame and genomic organization. SMAD5 transcripts are readily detectable in hematolymphoid tissues and leukemic blasts. Absence of intragenic mutations in the remaining SMAD5 allele of leukemic patients and multiple solid tumor cell lines prescreened for loss of heterozygosity suggests that SMAD5 may not be a common target of somatic inactivation in malignancy.
获得性5号染色体间质缺失或完全缺失是与白血病前期骨髓发育异常和急性髓性白血病相关的复发性异常，预后较差。先前的研究已将一个潜在的髓系肿瘤抑制基因座定位于5q31上IL9和EGR1基因之间<2.4-Mb的区间内。在本报告中，我们已将肿瘤抑制基因SMAD4/DPC-4和SMAD2/JV18.1的同源基因SMAD5定位于最小髓系肿瘤抑制基因座，并对其开放阅读框和基因组结构进行了表征。SMAD5转录本在血液淋巴组织和白血病原始细胞中易于检测到。对白血病患者剩余的SMAD5等位基因以及针对杂合性缺失进行预筛选的多种实体瘤细胞系进行基因内突变检测，结果表明SMAD5可能不是恶性肿瘤中体细胞失活的常见靶点。
