O'Briant K C, Bepler G
Department of Medicine, Duke University Medical Center, NC 27710, USA.
Genes Chromosomes Cancer. 1997 Feb;18(2):111-4. doi: 10.1002/(sici)1098-2264(199702)18:2<111::aid-gcc5>3.0.co;2-5.
We have reported frequent allele loss for two separate regions identified by the markers D11S12 and HRAS on chromosome 11p15.5. D11S12 allele loss was associated with tumor stage and type and HRAS allele loss with cigarette consumption, sex, and survival. To positionally clone the putative tumor suppressor genes located in these regions, we here report a reduction in the size of these intervals to approximately 250 kb. The markers used, ordered from centromere to telomere, were D11S932 -D11S1331-D11S1760-D11S1323-D11S4891 (HBB)-D11S1758-D11S12-D11S988-D11S860-D11S131 8-TH-HRAS-D11S1363-D11S2071. We analyzed 44 tissue pairs from patients with primary lung cancer. The smallest common regions of allele loss were located between D11S1758 and D11S12 in the centromeric region of chromosome segment 11p15.5 (region of LOH on chromosome 11 in lung cancer, LOH11A) and between HRAS and D11S1363 in the telomeric region (region of LOH on chromosome 11 in lung cancer, LOH11B). Loss of heterozygosity was observed in 24/39 (62%) primary lung cancers informative for LOH11A and in 17/34 (50%) informative for LOH11B. The pattern of allele loss strongly suggests that two lung cancer suppressor genes are located on chromosome segment 11p15.5, one between D11S1758 and D11S12 and the other between HRAS and D11S1363. The estimated physical size of each of these regions is 250 kb.
我们曾报道过，在11号染色体p15.5区域中，由标记D11S12和HRAS所确定的两个不同区域存在频繁的等位基因缺失。D11S12等位基因缺失与肿瘤分期和类型相关，而HRAS等位基因缺失与吸烟量、性别及生存率相关。为了通过定位克隆确定位于这些区域的假定肿瘤抑制基因，我们在此报告将这些区间的大小缩减至约250 kb。所使用的标记，从着丝粒到端粒依次为：D11S932 - D11S1331 - D11S1760 - D11S1323 - D11S4891（HBB）- D11S1758 - D11S12 - D11S988 - D11S860 - D11S1318 - TH - HRAS - D11S1363 - D11S2071。我们分析了44例原发性肺癌患者的组织样本对。等位基因缺失的最小共同区域位于11号染色体片段p15.5着丝粒区域的D11S1758和D11S12之间（肺癌11号染色体杂合性缺失区域，LOH11A）以及端粒区域的HRAS和D11S1363之间（肺癌11号染色体杂合性缺失区域，LOH11B）。在39例对LOH11A有信息价值的原发性肺癌中，24例（62%）观察到杂合性缺失；在34例对LOH11B有信息价值的病例中，17例（50%）观察到杂合性缺失。等位基因缺失模式强烈提示，两个肺癌抑制基因位于11号染色体片段p15.5上，一个在D11S1758和D11S12之间，另一个在HRAS和D11S1363之间。每个区域的估计物理大小为250 kb。
