Karkera J D, Ayache S, Ransome R J, Jackson M A, Elsayem A F, Sridhar R, Detera-Wadleigh S D, Wadleigh R G
Medical Oncology Section, Department of Veterans Affairs Medical Center, Washington, DC 20422, USA.
Clin Cancer Res. 2000 Sep;6(9):3565-9.
Esophageal cancer ranks among the 10 most common cancers worldwide and is almost invariably fatal. The detailed genetic repertoire involved in esophageal carcinogenesis has not been defined. We have shown previously that the esophageal squamous cell carcinoma genome exhibits a frequent loss of heterozygosity (LOH) in the pericentromeric region of chromosome 18. To construct a fine deletion map, we screened 76 new samples composed of microdissected esophageal squamous cell carcinoma and matched morphologically normal epithelial cells using closely spaced markers. Maximal LOH frequency (54%) was displayed by D18S542 on 18p11.2. The pattern of LOH in selected patients indicated that the short region of overlap extends 3 cM on either side of D18S542. On the long arm of chromosome 18, the highest frequency of allelic loss (42%) was detected by D18S978 on 18q12.2-q21.1. This analysis revealed a short region of overlap of approximately 0.8 cM. These findings further implicate unreported tumor suppressor genes encoded by 18p11.2 and 18q12.2 in esophageal squamous cell carcinogenesis and they indicate a refinement of their map location.
食管癌是全球十大常见癌症之一，几乎无一例外都是致命的。食管癌发生过程中涉及的详细基因组成尚未明确。我们之前已经表明，食管鳞状细胞癌基因组在18号染色体的着丝粒周围区域经常出现杂合性缺失（LOH）。为了构建一个精细的缺失图谱，我们使用紧密间隔的标记物筛选了76个新样本，这些样本由显微切割的食管鳞状细胞癌和形态学上匹配的正常上皮细胞组成。位于18p11.2的D18S542显示出最高的LOH频率（54%）。所选患者的LOH模式表明，重叠的短区域在D18S542两侧各延伸3厘摩。在18号染色体的长臂上，位于18q12.2 - q21.1的D18S978检测到最高的等位基因缺失频率（42%）。该分析揭示了一个约0.8厘摩的短重叠区域。这些发现进一步表明18p11.2和18q12.2编码的未报道的肿瘤抑制基因与食管鳞状细胞癌发生有关，并表明它们图谱位置的细化。
