Stilgenbauer S, Nickolenko J, Wilhelm J, Wolf S, Weitz S, Döhner K, Boehm T, Döhner H, Lichter P
Medizinische Klinik und Poliklinik V, Heidelberg, Germany.
Oncogene. 1998 Apr 9;16(14):1891-7. doi: 10.1038/sj.onc.1201764.
Deletions affecting the interval between the RB1 gene and marker D13S25 at band 13q14 are the most frequent genetic abnormalities of B-cell chronic lymphocytic leukemia (B-CLL) and indicate the presence of a novel tumor suppressor gene in this region. In the current study, a high resolution physical map of fragments spanning one megabasepair (Mb) of genomic DNA at the critical 13q14 segment was constructed. To define the minimal region of loss within the RB1 and D13S25 interval, we screened 322 B-CLLs for deletions at either of the two loci. Thirty mantle cell lymphomas (MCLs) were included in the analysis because we observed a 13q14 deletion pattern similar to B-CLL in this disease. The incidence of 13q14 deletions was 51% in B-CLL and 70% in MCL, respectively. No frequent loss of the BRCA2 gene at band 13q12 was found. Detailed deletion mapping at band 13q14 with probes from the RB1-D13S25 interval lead to the identification of a critical deletion region 400 kb in size. Within this region two segments were most frequently affected, one at D13S272 120 kb in size and another 240 kb distal of D13S272 80 kb in size. From these two segments expressed sequences were identified as candidates for the putative 13q14 tumor suppressor gene involved in the pathogenesis of B-CLL and MCL.
影响13q14带RB1基因与标记D13S25之间区域的缺失是B细胞慢性淋巴细胞白血病（B-CLL）最常见的遗传异常，表明该区域存在一个新的肿瘤抑制基因。在本研究中，构建了关键的13q14区段跨越1兆碱基对（Mb）基因组DNA片段的高分辨率物理图谱。为了确定RB1和D13S25区间内的最小缺失区域，我们在322例B-CLL中筛查了这两个位点之一的缺失情况。分析中纳入了30例套细胞淋巴瘤（MCL），因为我们在这种疾病中观察到与B-CLL相似的13q14缺失模式。13q14缺失的发生率在B-CLL中为51%，在MCL中为70%。未发现13q12带BRCA2基因的频繁缺失。用来自RB1-D13S25区间的探针在13q14带进行详细的缺失图谱分析，确定了一个大小为400 kb的关键缺失区域。在这个区域内，有两个区段最常受到影响，一个在D13S272，大小为120 kb，另一个在D13S272远端240 kb处，大小为80 kb。从这两个区段中鉴定出表达序列，作为参与B-CLL和MCL发病机制的假定13q14肿瘤抑制基因的候选基因。
