Microsatellite mutations in buccal cells are associated with aging and head and neck carcinoma.
Microsatellite mutations in buccal cells are associated with aging and head and neck carcinoma.
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DOI：
10.1038/sj.bjc.6604198
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发表时间：
2008-02-12
影响因子：
8.8
通讯作者：
Yarbrough, W. G.
中科院分区：
文献类型：
--
作者：
Slebos, R. J. C.;Li, M.;Vadivelu, S.;Burkey, B. B.;Netterville, J. L.;Sinard, R.;Gilbert, J.;Murphy, B.;Chung, C. H.;Shyr, Y;Yarbrough, W. G.
吸烟引起的致癌物质暴露是上呼吸消化道癌症的主要原因，但重度吸烟者一生中罹患其中一种癌症的风险仅为 10% 左右。目前的技术只能有限地预测癌症风险，并且没有经过批准的适用于一般人群的筛查方法。我们开发了一种使用小库 PCR (SP-PCR) 评估体细胞突变负荷的方法，并分析了从漱口水获得的细胞中分离的 DNA 突变。研究人员对 25 例头颈鳞状癌 (HNSCC) 病例和 31 例对照样本中的高可变四核苷酸标记物 D7S1482 的突变水平进行了分析，并测试了其与年龄、吸烟史和癌症状况的关联。我们发现突变频率与年龄之间存在显着相关性（P=0.021，广义线性模型（GLM），N=56），但吸烟史没有影响。当校正年龄的影响时，病例的突变频率高于对照组，这一差异在仅接受手术治疗的 10 名 HNSCC 患者亚组中具有统计学意义（P=0.017，GLM，N=41）。我们还提供了证据，表明癌症状态与 D7S1482 中非独特且可能是克隆衍生的突变水平有关。在 1058 个等位基因中，有 833 个（79%）观察到插入突变，其中 457 个（43%）可以通过单个重复单元的插入来解释；在 225 个 (21%) 的测试等位基因中发现了缺失突变。总之，我们证明通过 SP-PCR 敏感检测临床标本中的单分子突变是可行的。我们的研究证实了早期的报告，即微卫星突变随着年龄的增长而增加，并且是第一个提供这些突变可能与个体受试者的癌症状态相关的证据的研究。
Carcinogen exposure from tobacco smoking is the major cause of upper aerodigestive tract cancer, yet heavy smokers only have about a 10% life-time risk of developing one of these cancers. Current technologies allow only limited prediction of cancer risk and there are no approved screening methods applicable to the general population. We developed a method to assess somatic mutational load using small-pool PCR (SP-PCR) and analysed mutations in DNA isolated from cells obtained by mouth rinse. Mutation levels in the hypermutable tetranucleotide marker D7S1482 were analysed in specimens from 25 head and neck squamous carcinoma (HNSCC) cases and 31 controls and tested for associations with age, smoking history and cancer status. We found a significant association between mutation frequency and age (P=0.021, Generalized Linear Model (GLM), N=56), but no influence of smoking history. Cases had higher mutation frequencies than controls when corrected for the effects of age, a difference that was statistically significant in the subgroup of 10 HNSCC patients who were treated with surgery only (P=0.017, GLM, N=41). We also present evidence that cancer status is linked to levels of nonunique, and presumably clonally derived, mutations in D7S1482. Insertion mutations were observed in 833 (79%) of 1058 alleles, of which 457 (43%) could be explained by insertion of a single repeat unit; deletion mutations were found in 225 (21%) of tested alleles. In conclusion, we demonstrate that the sensitive detection of single molecule mutations in clinical specimens is feasible by SP-PCR. Our study confirms an earlier report that microsatellite mutations increase with age and is the first to provide evidence that these mutations may be associated with cancer status in individual subjects.
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影响因子：
64.8
作者：
Kovtun, Irina V.;Liu, Yuan;McMurray, Cynthia T.
通讯作者：
McMurray, Cynthia T.
DOI：
10.1016/j.mrgentox.2004.01.003
发表时间：
2004-04-11
影响因子：
1.9
作者：
Slebos, RJC;Little, RE;Taylor, JA
通讯作者：
Taylor, JA
影响因子：
4.4
作者：
Coolbaugh-Murphy, M;Maleki, A;Brown, BW
通讯作者：
Brown, BW
DOI：
10.1073/pnas.95.21.12468
发表时间：
1998-10-13
影响因子：
11.1
作者：
Jackson, AL;Chen, R;Loeb, LA
通讯作者：
Loeb, LA
影响因子：
4.7
作者：
Diem, C;Runger, TM
通讯作者：
Runger, TM