Samowitz W S, Slattery M L
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
Am J Pathol. 1997 Jul;151(1):33-5.
Frame-shift mutations in a run of 10 adenines (A10) of the transforming growth factor-beta receptor type 2 gene (TGF-beta RII) are commonly seen in inherited and sporadic colonic cancers that exhibit microsatellite instability. A10 mutations and instability also are commonly seen in hereditary nonpolyposis colon cancer-associated adenomas. However, instability is quite rare in sporadic adenomas, and the timing of acquisition of A10 mutations with respect to the sporadic adenoma-carcinoma sequence has not been reported. We evaluated 100 sporadic colorectal cancers and 164 sporadic adenomas for microsatellite instability with a set of 10 tetranucleotide polymerase chain reaction primer sets and for A10 frame-shift mutations. A10 mutations were significantly associated with microsatellite instability in colorectal cancers, being seen in 9 of 11 cancers with 50% or greater instability and in 0 of 89 tumors with less than 50% instability (P < 0.0001). A10 mutations were not detected in any adenomas, only three of which (1.8%) exhibited significant (30% or greater) instability. We conclude that both TGF-beta RII frame-shift mutations and microsatellite instability occur at a relatively late stage of sporadic colorectal tumorigenesis. A10 frame-shift mutations appear to be restricted to sporadic colorectal cancers with extensive microsatellite instability.
转化生长因子β受体2型基因（TGF-βRII）中一段10个腺嘌呤（A10）的移码突变在表现出微卫星不稳定性的遗传性和散发性结肠癌中很常见。A10突变和不稳定性在遗传性非息肉病性结肠癌相关腺瘤中也很常见。然而，散发性腺瘤中不稳定性相当罕见，并且关于散发性腺瘤-癌序列中A10突变获得的时间尚未见报道。我们使用一组10个四核苷酸聚合酶链反应引物对评估了100例散发性结直肠癌和164例散发性腺瘤的微卫星不稳定性以及A10移码突变。A10突变与结直肠癌中的微卫星不稳定性显著相关，在11例不稳定性为50%或更高的癌症中有9例出现A10突变，而在89例不稳定性低于50%的肿瘤中未发现A10突变（P<0.0001）。在任何腺瘤中均未检测到A10突变，其中只有3例（1.8%）表现出显著（30%或更高）的不稳定性。我们得出结论，TGF-βRII移码突变和微卫星不稳定性均发生在散发性结直肠癌发生的相对晚期。A10移码突变似乎仅限于具有广泛微卫星不稳定性的散发性结直肠癌。
