Tumorigenesis in colorectal tumors from patients with hereditary non-polyposis colorectal cancer
Tumorigenesis in colorectal tumors from patients with hereditary non-polyposis colorectal cancer
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DOI：
10.1007/s004390050585
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发表时间：
1997-11-01
期刊：
影响因子：
5.3
通讯作者：
Lindblom, A
中科院分区：
文献类型：
--
作者：
Tannergard, P;Liu, T;Lindblom, A
遗传性非息肉病性结直肠癌(HNPCC)患者的结直肠癌发生机制与散发性结直肠癌不同。HN-PCC相关肿瘤的一个特征是复制错误表型。我们研究了来自29个HNPCC或结直肠癌家族聚集性的8个新鲜冰冻和67个石蜡包埋的结直肠癌的肿瘤发生。通过使用基因内标记，hMLH1野生型等位基因的失活是通过杂合性丢失而不是体体点突变发生的，微卫星不稳定性是非常常见的，几乎所有HNPCC患者的结直肠肿瘤都会早期发生。转化生长因子βII型受体(TβRII)突变在这些肿瘤中发生的频率很高。在来自HNPCC家族的结直肠癌中，63%的人有TβRII移码突变，而散发性结直肠癌的这一比例为10%。APC和K-RAS突变在HNPCC肿瘤中的频率似乎与散发性相应的肿瘤一样频繁。
Tumorigenesis of colorectal cancer in patients with hereditary non-polyposis colorectal cancer (HNPCC) has been postulated to follow a different pathway from that of sporadic colorectal tumors. A characteristic of HN-PCC-asssociated tumors is the replication error phenotype. We studied tumorigenesis in 8 fresh-frozen and 67 paraffin-embedded colorectal tumors derived from 29 families with HNPCC or a familial aggregation of colorectal cancer. By using intragenic markers, inactivation of the wildtype allele of hMLH1 was shown to occur through loss of heterozygosity and not through a somatic point mutation, Microsatellite instability is very common and occurs early in almost all colorectal tumors from HNPCC patients. Transforming growth factor beta type II receptor (T beta RII) mutations occur in these tumors at a high frequency. Of colorectal cancers from families with HNPCC, 63% have frameshift mutations in T beta RII, compared with 10% of sporadic colorectal cancers. APC and K-RAS mutations appear to be as frequent in the HNPCC tumors as in the sporadic counterpart.