Infrequent Detection of Germline Allele-Specific Expression of TGFBR1 in Lymphoblasts and Tissues of Colon Cancer Patients
Infrequent Detection of Germline Allele-Specific Expression of TGFBR1 in Lymphoblasts and Tissues of Colon Cancer Patients
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DOI：
10.1158/0008-5472.can-09-0225
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发表时间：
2009-06-15
期刊：
影响因子：
11.2
通讯作者：
Markowitz, Sanford D.
中科院分区：
文献类型：
--
作者：
Guda, Kishore;Natale, Leanna;Markowitz, Sanford D.
最近，生殖系等位基因特异性表达（ASE）的基因编码的转化生长因子-I型受体（TGFBR 1）已被提出是一个主要的危险因素，在结肠癌的易感性。生殖系ASE导致TGFBR 1等位基因之一的表达降低（>1.5倍），并且显示在类似于20%的有信息的家族性和散发性结直肠癌（CRC）病例中发生。在本研究中，使用高定量焦磷酸测序技术，我们估计ASE的频率在一个队列的受影响的个人从家族性集群的晚期结肠肿瘤（癌症和腺瘤与高度异型增生），也从一个队列的个人散发CRC。如果显示等位基因表达比率1.5，则认为病例存在ASE阳性。使用来自淋巴母细胞系的RNA，我们发现，46信息高加索晚期结肠肿瘤的情况下，有家族史，只有2个人显示适度ASE，等位基因比分别为1.65和1.73。鉴于TGFBR 1的ASE（如果存在）在结肠中可能比其他组织更明显，我们还确定了来自散发性CRC病例正常结肠粘膜的RNA中TGFBR 1的等位基因比率。然而，我们在44例散发病例中没有发现ASE的证据。综上所述，我们发现，在结肠癌患者的淋巴母细胞和结肠上皮细胞中检测到的TGFBR 1的种系ASE是相对罕见的事件。[Cancer Res 2009;69（12）：4959-61]
Recently, germline allele-specific expression (ASE) of the gene encoding for transforming growth factor-type I receptor (TGFBR1) has been proposed to be a major risk factor for cancer predisposition in the colon. Germline ASE results in a lowered expression of one of the TGFBR1 alleles (>1.5-fold), and was shown to occur in similar to 20% of informative familial and sporadic colorectal cancer (CRC) cases. In the present study, using the highly quantitative pyrosequencing technique, we estimated the frequency of ASE in TGFBR1 in a cohort of affected individuals from familial clusters of advanced colon neoplasias (cancers and adenomas with high-grade dysplasia), and also from a cohort of individuals with sporadic CRCs. Cases were considered positive for the presence of ASE if demonstrating an allelic expression ratio 1.5. Using RNA derived from lymphoblastoid cell lines, we find that of 46 informative Caucasian advanced colon neoplasia cases with a family history, only 2 individuals display a modest ASE, with allelic ratios of 1.65 and 1.73, respectively. Given that ASE of TGFBR1, if present, would likely be more pronounced in the colon compared with other tissues, we additionally determined the allele ratios of TGFBR1 in the RNA derived from normal-appearing colonic mucosa of sporadic CRC cases. We, however, found no evidence of ASE in any of 44 informative sporadic cases analyzed. Taken together, we find that germline ASE of TGFBR1, as assayed in lymphoblastoid and colon epithelial cells of colon cancer patients, is a relatively rare event. [Cancer Res 2009;69(12):4959-61]