Uchino S, Tsuda H, Noguchi M, Yokota J, Terada M, Saito T, Kobayashi M, Sugimura T, Hirohashi S
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Cancer Res. 1992 Jun 1;52(11):3099-102.
We examined 28 cases of surgically resected gastric cancer, excluding the diffuse type, for loss of heterozygosity (LOH) on 12 chromosomal arms using polymorphic DNA markers. LOH on chromosome 18q was detected in 61% (14 of 23) of the cases by the probes OLVIIA8, OLVIIE10, p15-65, SAM 1.1, and OS-4, and a putative common region showing LOH included the locus of the DCC tumor suppressor gene. LOH on chromosome 17p was also frequently found (8 of 19 or 42% of the cases) by the probes p10-3 and pHF12-1, and in 5 of these 6 cases the LOH on chromosome 17p was accompanied by LOH on chromosome 18q. On the other hand, the incidence of LOH was 30% or less using probes pHRnES, pHF12-65, p-c-mybE2.6, NJ3 3.2, pHF12-8, pHINS6.0, p9D11, hp2-alpha, pCMM6, and P1A5 on chromosomes 1q, 5, 6q, 7q, 9, 11p, 13q, 16q, 20, and 22q, respectively. LOH on chromosome 18q was frequent irrespective of the depth of tumor invasion, whereas the incidence of LOH on chromosome 17p was higher in the cases in which the tumor invaded beyond the muscularis propria than in those in which tumor invasion was limited to the submucosa and muscularis propria. These results suggest that LOH on chromosome 18q occurs at an earlier stage than LOH on chromosome 17p and that the inactivation of tumor suppressor genes located on chromosome 17p and 18q (e.g., the p53 and DCC genes) is critically involved in the development of the majority of gastric cancers. While alteration of the p53 gene is observed in various human cancers, that of the DCC gene is considered to occur more selectively in gastrointestinal cancers.
我们使用多态性DNA标记，对28例手术切除的胃癌（不包括弥漫型）进行检测，以观察12条染色体臂上的杂合性缺失（LOH）情况。通过探针OLVIIA8、OLVIIE10、p15 - 65、SAM 1.1和OS - 4，在61%（23例中的14例）的病例中检测到18号染色体长臂上存在LOH，一个显示有LOH的假定共同区域包含DCC肿瘤抑制基因位点。通过探针p10 - 3和pHF12 - 1，也经常在17号染色体短臂上发现LOH（19例中的8例，占42%），在这8例中的6例中，17号染色体短臂上的LOH同时伴有18号染色体长臂上的LOH。另一方面，分别使用染色体1q、5、6q、7q、9、11p、13q、16q、20和22q上的探针pHRnES、pHF12 - 65、p - c - mybE2.6、NJ3 3.2、pHF12 - 8、pHINS6.0、p9D11、hp2 - alpha、pCMM6和P1A5检测到的LOH发生率均在30%及以下。无论肿瘤浸润深度如何，18号染色体长臂上的LOH都很常见，而肿瘤浸润超过固有肌层的病例中，17号染色体短臂上的LOH发生率高于肿瘤浸润仅限于黏膜下层和固有肌层的病例。这些结果表明，18号染色体长臂上的LOH比17号染色体短臂上的LOH发生得更早，并且位于17号染色体短臂和18号染色体长臂上的肿瘤抑制基因（如p53和DCC基因）的失活在大多数胃癌的发生中起关键作用。虽然在各种人类癌症中都观察到p53基因的改变，但DCC基因的改变被认为在胃肠道癌症中更具选择性地发生。
