Ryu B, Song J, Sohn T, Hruban R H, Kern S E
Department of Oncology, The Johns Hopkins Medical Institutes, Baltimore, Maryland 21231, USA.
Genomics. 2001 Feb 15;72(1):108-12. doi: 10.1006/geno.2000.6449.
A number of carcinomas show high frequency of loss of heterozygosity (LOH) at chromosome 8p, suggesting that putative tumor suppressor genes are present in this region. While searching for homozygous deletions in a panel of pancreatic and biliary tumors, we discovered a homozygous deletion at the microsatellite AFMa224wh5 in chromosome region 8p12-p21. We applied a six-step algorithm comprising germline analysis, breakpoint sequencing, population screening, online gene mapping, allelic discrimination of tumor-associated LOH, and family history analysis. The results indicated that the deletion was likely due to a normal 102-bp deletion polymorphism present in nearly 10% of the study population, not likely to involve a recessive cancer-associated gene. Researchers need to be aware that germline insertion/deletion polymorphisms can affect the results of positional cloning efforts in human neoplasms. This problem would be accentuated in studies of cell lines where a paired sample of constitutional DNA is often unavailable.
许多癌症在8号染色体短臂（8p）显示出高频杂合性缺失（LOH），这表明该区域存在假定的肿瘤抑制基因。在一组胰腺和胆管肿瘤中寻找纯合缺失时，我们在染色体区域8p12 - p21的微卫星AFMa224wh5处发现了一个纯合缺失。我们应用了一种六步算法，包括种系分析、断点测序、群体筛查、在线基因定位、肿瘤相关LOH的等位基因鉴别以及家族史分析。结果表明，该缺失可能是由于研究人群中近10%存在正常的102个碱基对的缺失多态性，不太可能涉及隐性癌症相关基因。研究人员需要意识到，种系插入/缺失多态性会影响人类肿瘤中定位克隆研究的结果。在经常无法获得配对的体质DNA样本的细胞系研究中，这个问题会更加突出。
