A 2.5-Mb transcript map of a tumor-suppressing subchromosomal transferable fragment from 11p15.5, and isolation and sequence analysis of three novel genes
A 2.5-Mb transcript map of a tumor-suppressing subchromosomal transferable fragment from 11p15.5, and isolation and sequence analysis of three novel genes
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DOI：
10.1006/geno.1997.4981
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发表时间：
1997-11-15
期刊：
影响因子：
4.4
通讯作者：
Feinberg, AP
中科院分区：
文献类型：
--
作者：
Hu, RJ;Lee, MP;Feinberg, AP
11p15.5是一个重要的肿瘤抑制基因区域，在肾母细胞瘤、横纹肌肉瘤、肾上腺皮质癌以及肺癌、卵巢癌和乳腺癌中表现出杂合性缺失。我们之前通过遗传互补直接绘制了含有胚胎肿瘤抑制基因的亚可转移片段（STF），长度约为2.5 Mb。我们现在绘制了该STF的着丝粒端在D11S988和D11S12之间，其端粒端在D11S1318和TH之间。我们在这个STF定义的整个2.5 mb区域内分离出了完整的PAC、P1、BAG和cosmid基因组克隆，并使用外显子捕获技术从这些基因组克隆中分离出了200多个外显子。我们通过直接筛选cDNA文库和数据库搜索ESTs，分离到了该区域的基因。这些基因中有9个已经被我们和其他人报道过。然而，大多数这些基因的初始定位是基于FISH或体细胞杂交分析，在这里我们精确地定义了它们的物理位置。这些基因包括RRM1、GOK （D11S4896E）、Nup98、CARS、hNAP2 （NAP1LA）、p57(KIP2) （CDKN1C）、K(V)LQT1 （KCNA9）、TAPA-1和ASCL2。此外，我们在该区域发现了几个新基因，其中三个被称为TSSC1， TSSC2和TSSC3，在这里被报道。TSSC1与rb相关蛋白p48和染色质组装因子CAF1具有同源性，位于GOK和Nup98之间。TSSC2与秀丽隐杆线虫β -甘露糖基转移酶同源，位于Nup98和CARS之间。TSSC3与小鼠TDAG51具有同源性，TDAG51与快速介导的细胞凋亡有关，位于hNAP2和p57（KIP2）之间。因此，这些基因可能在涉及该区域的恶性肿瘤中发挥作用。(C) 1997学术出版社。
11p15.5 is an important tumor-suppressor gene region, showing loss of heterozygosity in Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. We previously mapped directly by genetic complementation a subtransferable fragment (STF) harboring an embryonal tumor-suppressor gene and spanning about 2.5 Mb. We have now mapped the centromeric end of this STF between D11S988 and D11S12 and its telomeric end between D11S1318 and TH. We have isolated a complete contig of PAC, P1, BAG, and cosmid genomic clones spanning the entire 2.5-Mb region defined by this STF, as well as more than 200 exons from these genomic clones using exon trapping. We have isolated genes in this region by directly screening cDNA libraries as well as by database searching for ESTs. Nine of these genes have been reported previously by us and by others. However, the initial mapping of most of those genes was based on FISH or somatic cell hybrid analysis, and here we precisely define their physical location. These genes include RRM1, GOK (D11S4896E), Nup98, CARS, hNAP2 (NAP1LA), p57(KIP2) (CDKN1C), K(V)LQT1 (KCNA9), TAPA-1, and ASCL2. Ln addition, we have identified several novel genes in this region, three of which, termed TSSC1, TSSC2, and TSSC3, are reported here. TSSC1 shows homology to Rb-associated protein p48 and chromatin assembly factor CAF1, and it is located between GOK and Nup98. TSSC2 is homologous to Caenorhabditis elegans beta-mannosyl transferase, and it lies between Nup98 and CARS. TSSC3 shows homology to mouse TDAG51, which is implicated in Fast-mediated apoptosis, and it is located between hNAP2 and p57(KIP2). Thus, these genes may play a role in malignancies that involve this region. (C) 1997 Academic Press.