Beltinger C P, White P S, Maris J M, Sulman E P, Jensen S J, LePaslier D, Stallard B J, Goeddel D V, de Sauvage F J, Brodeur G M
Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104-4318, USA.
Genomics. 1996 Jul 1;35(1):94-100. doi: 10.1006/geno.1996.0327.
The tumor necrosis factor receptor 2 (TNFR2) gene localizes to 1p36. 2, a genomic region characteristically deleted in neuroblastomas and other malignancies. In addition, TNFR2 is the principal mediator of the effects of TNF on cellular immunity, and it may cooperate with TNFR1 in the killing of nonlymphoid cells. Therefore, we undertook an analysis of the genomic structure and precise physical mapping of this gene. The TNFR2 gene is contained on 10 exons that span 26 kb. Most of the functional domains of TNFR2 are encoded by separate exons, and each of the repeats of the extracellular cysteine-rich domain is interrupted by an intron. The genomic structure reveals a close relationship to TNFR1, another member of the TNFR superfamily. Based on electrophoretic analysis of yeast artificial chromosomes, TNFR2 maps within 400 kb of the genetic marker D1S434. In addition, we have identified a new polymorphic dinucleotide repeat within intron 4 of TNFR2. The genetic sequence information and exon-intron boundaries we have determined will facilitate mutational analysis of this gene to determine its potential role in neuroblastoma, as well as in other cancers with characteristic deletions or rearrangements of 1p36.
肿瘤坏死因子受体2（TNFR2）基因定位于1p36.2，这是一个在神经母细胞瘤和其他恶性肿瘤中特征性缺失的基因组区域。此外，TNFR2是TNF对细胞免疫作用的主要介质，并且它可能在杀伤非淋巴细胞方面与TNFR1协同作用。因此，我们对该基因的基因组结构和精确物理图谱进行了分析。TNFR2基因由跨越26kb的10个外显子组成。TNFR2的大多数功能结构域由单独的外显子编码，并且细胞外富含半胱氨酸结构域的每个重复序列都被一个内含子中断。基因组结构揭示了与TNFR超家族的另一个成员TNFR1的密切关系。基于酵母人工染色体的电泳分析，TNFR2定位于遗传标记D1S434的400kb范围内。此外，我们在TNFR2的内含子4中鉴定出一个新的多态性二核苷酸重复序列。我们确定的遗传序列信息和外显子 - 内含子边界将有助于对该基因进行突变分析，以确定其在神经母细胞瘤以及其他具有1p36特征性缺失或重排的癌症中的潜在作用。
