Sasaki M
Fukuoka Igaku Zasshi. 1989 Jan;80(1):38-48.
Familial polyposis coli (FPC) is a genetic disorder, transmitted as an autosomal dominant trait, characterized by numerous colorectal adenomas. If untreated, most patients may develop colorectal adenocarcinomas. We investigated linkage between FPC and several DNA markers, and loss of heterozygosity in colorectal tumors by using RFLP analysis. We examined 15 pedigrees for linkage analysis and 31 FPC patients including 16 adenocarcinomas and 43 adenomas and 15 non-polyposis colorectal carcinomas (NPCC) for searching loss of heterozygosity. 1. Significant linkage was not observed with 26 polymorphic DNA probes. Maximum lod score of 0.301 at a recombination fraction of 0.0 was observed with the marker D5S71, which was reported to be tightly linked to the major gene for FPC in Caucasian. 2. Loss of heterozygosity was observed at the loci on 17 chromosomes in colorectal carcinomas from FPC patients, and on 6 chromosomes in NPCC. Thus, chromosomes in FPC patients may be unstable compared with those in patients with NPCC. 3. Frequent loss of heterozygosity in colorectal carcinomas from FPC patients was observed on chromosomes 5 (20%), 14 (22%), 17 (43%) and 22 (38%), and was also observed on chromosomes 5 (33%), 14 (38%), 17 (27%) and 22 (15%) in NPCC. These results suggest that tumor suppression genes may locate on these chromosomes. 4. Tumor suppression genes may play a role by dose dependent way.
家族性腺瘤性息肉病（FPC）是一种遗传性疾病，以常染色体显性性状遗传，其特征为大量结肠直肠腺瘤。若不治疗，大多数患者可能会发展为结肠直肠癌。我们通过限制性片段长度多态性（RFLP）分析研究了FPC与几种DNA标记之间的连锁关系以及结肠直肠肿瘤中的杂合性缺失情况。我们检查了15个家系进行连锁分析，并检查了31例FPC患者，包括16例腺癌、43例腺瘤和15例非息肉病性结肠直肠癌（NPCC）以寻找杂合性缺失。1. 未观察到与26个多态性DNA探针的显著连锁。在标记D5S71处，重组率为0.0时观察到最大对数优势得分为0.301，据报道该标记在白种人中与FPC的主要基因紧密连锁。2. 在FPC患者的结肠直肠癌中，观察到17号染色体上的位点存在杂合性缺失，在NPCC中观察到6号染色体上存在杂合性缺失。因此，与NPCC患者相比，FPC患者的染色体可能不稳定。3. 在FPC患者的结肠直肠癌中，观察到5号染色体（20%）、14号染色体（22%）、17号染色体（43%）和22号染色体（38%）上频繁出现杂合性缺失，在NPCC中5号染色体（33%）、14号染色体（38%）、17号染色体（27%）和22号染色体（15%）上也观察到杂合性缺失。这些结果表明肿瘤抑制基因可能位于这些染色体上。4. 肿瘤抑制基因可能以剂量依赖方式发挥作用。
