PTCH mutations in basal cell carcinomas from azathioprine-treated organ transplant recipients.
PTCH mutations in basal cell carcinomas from azathioprine-treated organ transplant recipients.
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DOI：
10.1038/sj.bjc.6604665
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发表时间：
2008-10-21
影响因子：
8.8
通讯作者：
Karran, P.
中科院分区：
文献类型：
--
作者：
Harwood, C. A.;Attard, N. R.;Donovan, P. O';Chambers, P.;Perrett, C. M.;Proby, C. M.;McGregor, J. M.;Karran, P.
免疫抑制剂硫唑嘌呤用于预防器官移植后的移植物排斥。为了调查硫唑嘌呤相关诱变是否导致器官移植受者 (OTR) 皮肤肿瘤的高发病率，我们分析了 60 例基底细胞癌 (BCC) 中的 PTCH 基因突变； 39 例来自接受硫唑嘌呤的 OTR，21 例来自从未接触过硫唑嘌呤的个体。 55% 的肿瘤中 PTCH 发生突变，与硫唑嘌呤治疗无关。在硫唑嘌呤和非硫唑嘌呤组中，二嘧啶序列的转变（被认为表明 UV-B 辐射引起的突变）经常发生在长期暴露在阳光下的皮肤的肿瘤中。在接受硫唑嘌呤治疗的患者非日晒皮肤的基底细胞癌中，非二嘧啶位点存在过多的异常 G:C 到 A:T 转变。这些是硫唑嘌呤暴露组所独有的，并且全部处于 PTCH 内不同位置的相同 TGTC 序列背景中。对已发表研究中的 247 个 BCC 进行荟萃分析表明，这些突变在散发性 BCC 中很少见，并且以前从未在该特定序列背景下报道过。这项移植后 BCC 的研究首次表明硫唑嘌呤暴露可能与 PTCH 突变有关，特别是在非日晒皮肤肿瘤中。
The immunosuppressant azathioprine is used to prevent graft rejection after organ transplantation. To investigate whether azathioprine-associated mutagenesis contributes to the high incidence of skin tumours in organ transplant recipients (OTRs), we analysed PTCH gene mutations in 60 basal cell carcinomas (BCC); 39 from OTRs receiving azathioprine and 21 from individuals never exposed to azathioprine. PTCH was mutated in 55% of all tumours, independent of azathioprine treatment. In both the azathioprine and non-azathioprine groups, transitions at dipyrimidine sequences, considered to indicate mutation by ultraviolet-B radiation, occurred frequently in tumours from chronically sun-exposed skin. In BCC from non-sun-exposed skin of azathioprine-treated patients, there was an over-representation of unusual G:C to A:T transitions at non-dipyrimidine sites. These were exclusive to the azathioprine-exposed group and all in the same TGTC sequence context at different positions within PTCH. Meta-analysis of 247 BCCs from published studies indicated that these mutations are rare in sporadic BCC and had never previously been reported in this specific sequence context. This study of post-transplant BCC provides the first indication that azathioprine exposure may be associated with PTCH mutations, particularly in tumours from non-sun-exposed skin.
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硫唑嘌呤和UVA光产生诱变的氧化DNA损伤。
DOI：
10.1126/science.1114233
发表时间：
2005-09-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
O'Donovan P;Perrett CM;Zhang X;Montaner B;Xu YZ;Harwood CA;McGregor JM;Walker SL;Hanaoka F;Karran P
通讯作者：
Karran P
影响因子：
6.5
作者：
Eichberger, T;Regl, G;Frischauf, AM
通讯作者：
Frischauf, AM
影响因子：
13.8
作者：
Harwood, CA;Proby, CM;Cerio, R
通讯作者：
Cerio, R
影响因子：
10.3
作者：
Ismail, F.;Mitchell, L.;Harwood, C. A.
通讯作者：
Harwood, C. A.
影响因子：
--
作者：
Kanitakis, J;Alhaj-Ibrahim, L;Claudy, A
通讯作者：
Claudy, A