Identification of new minimally lost regions on 18q in head and neck squamous cell carcinoma.
Identification of new minimally lost regions on 18q in head and neck squamous cell carcinoma.
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发表时间：
2000-07
期刊：
影响因子：
11.2
通讯作者：
S. Takebayashi;T. Ogawa;K. Jung;A. Muallem;H. Mineta;S. Fisher;R. Grénman;T. Carey
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作者：
S. Takebayashi;T. Ogawa;K. Jung;A. Muallem;H. Mineta;S. Fisher;R. Grénman;T. Carey
18q 杂合性缺失 (LOH) 预示头颈鳞状细胞癌 (HNSCC) 的生存率较差。一些假定的肿瘤抑制基因，如 DCC、DPC4/Smad4 和 MADR2/Smad2，被定位到 18q，但迄今为止，HNSCC 中的重要基因位点尚不清楚。为了确定 18q 上可能的基因位点，我们使用来自 57 个 HNSCC 原代肿瘤细胞系的肿瘤 DNA 和从同一患者的成纤维细胞或类淋巴母细胞中分离的 DNA 进行了 LOH 研究。使用了 42 个高度多态性微卫星标记，其间隔不超过 5 cM（平均距离，1.82 cM），跨越从 18q11.1 中的 D18S44 到 18q23 中的 D18S1141 的区域。 18p11.21的D18S71也被用来判断是否保留短臂。 57 个 HNSCC 系中的 43 个 (75%) 在 18q 上至少有一个基因座显示 LOH 或孤立的等位基因不平衡 (AI)。尽管许多细胞系具有较大的远端 18q 缺失，并在 18q11.1 和 18q12.2 之间存在断点，但在 70% 或更多的病例中发现了三个基因座丢失。最小丢失区域 (MLR) 的大小范围为 1.5-15.79 cM。最近端集中在带 18q21.1 中的 D18S39 (1.56 cM)，在 38 例信息丰富的病例中，有 28 例 (74%) 存在 LOH 或孤立的 AI。最大的 (15.8 cM) 始于带 18q22.2 中的 D18S61（40 个中的 28 个；70%），并延伸至 18q23 中的 D18S50。第三个以 D18S70（40 个中的 30 个；75%）为中心，位于带 18q23 (3.67 cM) 中。在这些 MLR 中，只有以 D18S39 为中心的 MLR 此前曾与 HNSCC 相关。 D18S70 是最常丢失的标记物，是 UM-SCC-19、UM-SCC-67 和 UM-SCC-73A 三种肿瘤细胞系中唯一持续丢失且丢失量极小的标记物。此外，UM-SCC-91仅在该位点表现出AI，而UT-SCC-4仅在D18S70和D18S39表现出AI。这三个区域的紧密物理图谱可以查明一种或多种先前未识别的肿瘤抑制基因。
Loss of heterozygosity (LOH) on 18q predicts poor survival in head and neck squamous cell carcinomas (HNSCCs). Several putative tumor suppressor genes, such as DCC, DPC4/Smad4, and MADR2/Smad2, are mapped to 18q, but thus far, the important gene locus in HNSCC is not known. To identify possible gene loci on 18q, we performed LOH studies using tumor DNA from 57 HNSCC primary tumor cell lines and DNA isolated from fibroblasts or lymphoblastoid cells from the same patients. Forty-two highly polymorphic microsatellite markers spaced not more than 5 cM apart (mean distance, 1.82 cM) spanning the region from D18S44 in 18q11.1 to D18S1141 in 18q23 were used. D18S71 in 18p11.21 on 18p was also used to determine whether the short arm was retained. Forty-three of 57 (75%) HNSCC lines showed LOH or isolated allelic imbalance (AI) for at least one locus on 18q. Although many of the cell lines had large distal 18q deletions with a breakpoint between 18q11.1 and 18q12.2 to qter, three loci were identified that were lost in 70% or more of the cases. The minimally lost regions (MLRs) range in size from 1.5-15.79 cM. The most proximal is centered on D18S39 (1.56 cM) in band 18q21.1, with LOH or isolated AI in 28 of 38 (74%) of informative cases. The largest (15.8 cM) begins at D18S61 (28 of 40; 70%) in band 18q22.2 and extends through D18S50 in 18q23. The third is centered on D18S70 (30 of 40; 75%) in band 18q23 (3.67 cM). Of these MLRs, only the one centered on D18S39 has been implicated previously in HNSCC. D18S70, the most frequently lost marker, was the only marker consistently lost in three tumor cell lines with very minimal losses, UM-SCC-19, UM-SCC-67, and UM-SCC-73A. In addition, UM-SCC-91 exhibited AI only at this locus, and UT-SCC-4 had AI at D18S70 and D18S39 only. Close physical mapping of these three regions may pinpoint one or more previously unidentified tumor suppressor genes.