Yoshimoto K, Iizuka M, Iwahana H, Yamasaki R, Saito H, Saito S, Sekiya T
Oncogene Division, National Cancer Center Research Institute, Tokyo, Japan.
Cancer Res. 1989 May 15;49(10):2716-21.
The DNAs from two independent pancreatic cancers (tumors 1 and 2) in a patient with multiple endocrine neoplasia type 1 were analyzed. No amplification or gross rearrangement of 19 protooncogenes was observed. However, Southern blot analysis using polymorphic DNA probes revealed loss of heterozygosity at loci on chromosome 11p in both tumors. In tumor 1, an extensive region including the HRAS1, PTH, CALCA, and D11S151 loci was deleted, while in tumor 2 loss of heterozygosity was limited at the HRAS1 and D11S151 loci. Because loss of heterozygosity at other chromosomal loci in the two tumors was quite rare, loss of genes on 11p might be nonrandom. It is noteworthy that the same allele at the HRAS1 locus and also the same allele at the D11S151 locus were lost in the two independent tumors. These results suggest that loss of genes at the HRAS1 and/or D11S151 loci plays an important role unmasking the remaining sequences probably having a recessive mutation.
对一名患有1型多发性内分泌肿瘤患者的两个独立胰腺癌(肿瘤1和肿瘤2)的DNA进行了分析。未观察到19种原癌基因的扩增或大片段重排。然而,使用多态性DNA探针的Southern印迹分析显示,两个肿瘤中11号染色体短臂上的位点均出现杂合性缺失。在肿瘤1中,包括HRAS1、PTH、CALCA和D11S151位点的大片区域被缺失,而在肿瘤2中,杂合性缺失仅限于HRAS1和D11S151位点。由于两个肿瘤中其他染色体位点的杂合性缺失非常罕见,11号染色体短臂上的基因缺失可能是非随机的。值得注意的是,在两个独立的肿瘤中,HRAS1位点的相同等位基因以及D11S151位点的相同等位基因均缺失。这些结果表明,HRAS1和/或D11S151位点的基因缺失在揭示可能具有隐性突变的其余序列方面起着重要作用。