White P S, Thompson P M, Seifried B A, Sulman E P, Jensen S J, Guo C, Maris J M, Hogarty M D, Allen C, Biegel J A, Matise T C, Gregory S G, Reynolds C P, Brodeur G M
Division of Oncology, Children's Hospital of Philadelphia, Pennsylvania 19104-4318, USA.
Med Pediatr Oncol. 2001 Jan;36(1):37-41. doi: 10.1002/1096-911X(20010101)36:1<37::AID-MPO1010>3.0.CO;2-L.
Several lines of evidence es tablish that chromosome band 1p36 is frequently deleted in neuroblastoma primary tumors and cell lines, suggesting that a tumor suppressor gene within this region is involved in the development of this tumor.
We analyzed the status of 1p36 in primary neuroblastomas and cell lines to define the region of consistent rearrangement.
Loss of heterozygosity (LOH) studies of primary neuro blastomas identified allelic loss in 135 of 503 tumors (27%), with the smallest region of overlap (SRO) defined distal to D15214 (1p36.3). No homozygous deletions were detected at 120 loci mapping to 1p36.1-p36.3 in a panel of 46 neuroblastoma cell lines. A recently identified patient with neuroblastoma was found to have a constitutional deletion within 1p36.2-p36.3, and this deletion, when combined with the LOH results, defined a smaller SRO of one megabase within 1p36.3. We constructed a comprehensive integrated map of chromosome 1 containing 11,000 markers and large-insert clones, a high-resolution radiation hybrid (RH) map of 1p36, and a P1-artificial chromosome (PAC) contig spanning the SRO, to further characterize the region of interest. Over 768 kb (75%) of the SRO has been sequenced to completion. Further analysis of distal 1p identified 113 transcripts localizing to 1p36, 21 of which were mapped within the SRO.
This analysis will identify suitable positional candidate transcripts for mutational screening and subsequent identification of the 1p36.3 neuroblastoma suppressor gene.
多项证据表明，染色体1p36区在神经母细胞瘤原发肿瘤和细胞系中经常发生缺失，提示该区域内的一个肿瘤抑制基因参与了此肿瘤的发生发展。
我们分析了原发神经母细胞瘤和细胞系中1p36的状态，以确定一致重排的区域。
对原发神经母细胞瘤的杂合性缺失（LOH）研究发现，503例肿瘤中有135例（27%）存在等位基因缺失，最小重叠区域（SRO）定位于D15214（1p36.3）远端。在一组46个神经母细胞瘤细胞系中，映射到1p36.1 - p36.3的120个位点未检测到纯合缺失。发现一名新诊断的神经母细胞瘤患者在1p36.2 - p36.3区域存在先天性缺失，将此缺失与LOH结果相结合，确定了1p36.3内一个较小的1兆碱基SRO。我们构建了包含11,000个标记和大插入片段克隆的1号染色体综合整合图谱、1p36的高分辨率辐射杂种（RH）图谱以及跨越SRO的P1人工染色体（PAC）重叠群，以进一步表征感兴趣的区域。SRO超过768 kb（75%）已完成测序。对1p远端的进一步分析确定了113个转录本定位于1p36，其中21个映射在SRO内。
该分析将确定合适的位置候选转录本用于突变筛查以及随后鉴定1p36.3神经母细胞瘤抑制基因。
