Relationship of EMAST and microsatellite instability among patients with rectal cancer.
Relationship of EMAST and microsatellite instability among patients with rectal cancer.
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DOI：
10.1007/s11605-010-1340-6
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发表时间：
2010-10
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影响因子：
--
通讯作者：
Carethers JM
中科院分区：
文献类型：
--
作者：
Devaraj B;Lee A;Cabrera BL;Miyai K;Luo L;Ramamoorthy S;Keku T;Sandler RS;McGuire KL;Carethers JM
选定的四核苷酸重复序列（EMAST）的微卫星不稳定性升高是60%的散发性结肠癌中鉴定的遗传特征，可能与DNA错配修复（MMR）蛋白hMSH 3的异质性表达有关。与微卫星不稳定性高（MSI-H）不同，在MSI-H中，hMLH 1发生超甲基化，随后发生多个易感基因突变，EMAST可能与炎症和随后的MMR功能松弛相关，其生物学后果尚不清楚。由于EMAST在直肠癌中尚未确定，我们在一个基于人群的直肠癌队列中评估了EMAST和MSI的患病率。我们分析了147例散发性直肠癌使用五个四核苷酸微卫星标记和国家癌症研究所推荐的MSI（单核苷酸和二核苷酸）标记。EMAST和MSI测定是在聚合酶链反应产物的DNA序列分析上进行的，并且如果在来自同一患者的正常和癌症样品之间进行比较时发现至少两个基因座具有移码重复，则确定为阳性。我们将EMAST数据与种族、性别和肿瘤分期相关联，并检查了淋巴细胞浸润的样本。在该直肠癌患者队列中（平均年龄62.2 ± 10.3岁，36%女性，24%非裔美国人），3/147（2%）例患者显示MSI（3例男性，2例非裔美国人），49/147（33%）例患者显示EMAST。非裔美国人的直肠肿瘤比白人更可能显示EMAST（18/37，49% vs. 27/104，26%，p = 0.014），并且与晚期相关（18/29，62% EMAST vs. 18/53，37%，非EMAST p = 0.02）。EMAST与性别无关。与无肿瘤浸润的直肠肿瘤相比，EMAST在显示肿瘤周围浸润的直肠肿瘤中更常见（30/49，60% EMAST vs. 24/98，25% non-EMAST，p = 0.0001）。EMAST在直肠癌中很常见，MSI很少见。EMAST与非洲裔美国人种族相关，可能更常见于转移性疾病。EMAST的病因和后果正在研究中，但其与免疫细胞浸润的相关性表明炎症可能在其发展中起作用。
Elevated microsatellite instability at selected tetranucleotide repeats (EMAST) is a genetic signature identified in 60% of sporadic colon cancers and may be linked with heterogeneous expression of the DNA mismatch repair (MMR) protein hMSH3. Unlike microsatellite instability-high (MSI-H) in which hypermethylation of hMLH1 occurs followed by multiple susceptible gene mutations, EMAST may be associated with inflammation and subsequent relaxation of MMR function with the biological consequences not known. We evaluated the prevalence of EMAST and MSI in a population-based cohort of rectal cancers, as EMAST has not been previously determined in rectal cancers. We analyzed 147 sporadic cases of rectal cancer using five tetranucleotide microsatellite markers and National-Cancer-Institute-recommended MSI (mononucleotide and dinucleotide) markers. EMAST and MSI determinations were made on analysis of DNA sequences of the polymerase chain reaction products and determined positive if at least two loci were found to have frame-shifted repeats upon comparison between normal and cancer samples from the same patient. We correlated EMAST data with race, gender, and tumor stage and examined the samples for lymphocyte infiltration. Among this cohort of patients with rectal cancer (mean age 62.2 ± 10.3 years, 36% female, 24% African American), 3/147 (2%) showed MSI (three males, two African American) and 49/147 (33%) demonstrated EMAST. Rectal tumors from African Americans were more likely to show EMAST than Caucasians (18/37, 49% vs. 27/104, 26%, p = 0.014) and were associated with advanced stage (18/29, 62% EMAST vs. 18/53, 37%, non-EMAST p = 0.02). There was no association between EMAST and gender. EMAST was more prevalent in rectal tumors that showed peri-tumoral infiltration compared to those without (30/49, 60% EMAST vs. 24/98, 25% non-EMAST, p = 0.0001). EMAST in rectal cancer is common and MSI is rare. EMAST is associated with African-American race and may be more commonly seen with metastatic disease. The etiology and consequences of EMAST are under investigation, but its association with immune cell infiltration suggests that inflammation may play a role for its development.
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影响因子：
8
作者：
Catto, JWF;Azzouzi, AR;Meuth, M
通讯作者：
Meuth, M
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2.8
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4.5
作者：
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