CLUES TO THE PATHOGENESIS OF FAMILIAL COLORECTAL-CANCER
CLUES TO THE PATHOGENESIS OF FAMILIAL COLORECTAL-CANCER
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DOI：
10.1126/science.8484121
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发表时间：
1993-05-07
期刊：
影响因子：
56.9
通讯作者：
DELACHAPELLE, A
中科院分区：
文献类型：
--
作者：
AALTONEN, LA;PELTOMAKI, P;DELACHAPELLE, A
在某些家族中，结直肠癌的易感性与2号染色体上的标记有关。家族性结肠癌的分子特征与散发性结肠癌的分子特征进行了比较。家族性或散发性癌症均未显示2号染色体标记物杂合性丢失，两组肿瘤中KRAS、P53和APC突变的发生率相似。然而，大多数家族性癌症在短重复DNA序列中有广泛的改变，这表明在肿瘤发展过程中发生了许多复制错误。13%的散发性癌症具有相同的异常，这些癌症与家族性病例具有相同的生物学特性。这些数据表明，家族性肿瘤发生的机制不同于经典的肿瘤抑制基因介导的。
A predisposition to colorectal cancer is shown to be linked to markers on chromosome 2 in some families. Molecular features of ''familial'' cancers were compared with those of sporadic colon cancers. Neither the familial nor sporadic cancers showed loss of heterozygosity for chromosome 2 markers, and the incidence of mutations in KRAS, P53, and APC was similar in the two groups of tumors. Most of the familial cancers, however, had widespread alterations in short repeated DNA sequences, suggesting that numerous replication errors had occurred during tumor development. Thirteen percent of sporadic cancers had identical abnormalities and these cancers shared biologic properties with the familial cases. These data suggest a mechanism for familial tumorigenesis different from that mediated by classic tumor suppressor genes.