Single nucleotide polymorphism rs17849071 G/T in the PIK3CA gene is inversely associated with follicular thyroid cancer and PIK3CA amplification.
Single nucleotide polymorphism rs17849071 G/T in the PIK3CA gene is inversely associated with follicular thyroid cancer and PIK3CA amplification.
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DOI：
10.1371/journal.pone.0049192
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Trink B
中科院分区：
文献类型：
--
作者：
Xing JC;Tufano RP;Murugan AK;Liu D;Wand G;Ladenson PW;Xing M;Trink B
原癌基因PIK3CA在甲状腺癌中的激活突变和基因组扩增已经得到了很好的研究，但单核苷酸多态性（SNP）尚未得到研究。我们对503例甲状腺肿瘤患者的PIK3CA SNP rs17849071（小等位基因G和大等位基因T）进行了PCR检测，并对携带该SNP的9号内含子区域进行了测序。该SNP在正常和甲状腺肿瘤组织以及所研究家族的不同代中都被发现，证实了它是甲状腺肿瘤患者的种系遗传事件。与正常受试者相比，滤泡性甲状腺癌（FTC）患者中rs17849071杂合基因型G/T的患病率显著降低。其中，正常受试者中有15%（18/117）存在rs17849071G/T， FTC患者中有1.3%（1/77）存在rs17849071G/T，比值比为0.07 （95% CI 0.01-0.55; P = 0.001）。这意味着携带这种SNP的FTC风险降低了93%。相比之下，良性甲状腺肿瘤中rs17849071G/T的患病率为13.1%(17/130)，比值比为0.83 （95% CI 0.40-1.69; P = 0.72）。rs17849071G/T在其他类型甲状腺癌中的患病率和比值比均有降低的趋势，但无统计学意义。我们还发现rs17849071G/T与PIK3CA扩增呈有趣的反比关系。当拷贝数≥4定义为拷贝增益时，2.9% (1/34)rs17849071G/T对19.0% (67/352)rs17849071T/T显示PIK3CA扩增（P = 0.01）。相反，PIK3CA扩增的病例中有1.5%（1/68）携带rs17849071G/T，而未PIK3CA扩增的病例中有10.4%（33/318）携带rs17849071G/T （P = 0.01）。这就解释了rs17849071G/T与FTC的互反关系，因为PIK3CA扩增是甲状腺癌，尤其是FTC的重要致癌机制。因此，本研究发现了一个有趣的现象，rs17849071G/T可能通过阻止PIK3CA扩增而对FTC具有保护作用。
The proto-oncogene PIK3CA has been well studied for its activating mutations and genomic amplifications but not single nucleotide polymorphism (SNP) in thyroid cancer. We investigated SNP rs17849071 (minor allele G and major allele T) in PIK3CA in thyroid tumors in 503 subjects by PCR and sequencing of a region of intron 9 carrying this SNP. This SNP was found in both normal and thyroid tumor tissues as well as in different generations of a studied family, confirming it to be a germline genetic event in thyroid tumor patients. In comparison with normal subjects, a dramatically lower prevalence of the heterozygous genotype G/T at rs17849071 was found in patients with follicular thyroid cancer (FTC). Specifically, rs17849071G/T was found in 15% (18/117) normal subjects vs. 1.3% (1/77) FTC patients, with an odds ratio of 0.07 (95% CI 0.01–0.55; P = 0.001). This represents a 93% risk reduction for FTC with this SNP. In contrast, no difference was seen with benign thyroid neoplasms in which the prevalence of rs17849071G/T was 13.1% (17/130), with an odds ratio of 0.83 (95% CI 0.40–1.69; P = 0.72). There was a trend of lower prevalences of rs17849071G/T and odds ratio in other types of thyroid cancer without statistical significance. We also found an interesting inverse relationship of rs17849071G/T with PIK3CA amplification. With copy number ≥4 defined as copy gain, 2.9% (1/34) rs17849071G/T vs. 19.0% (67/352) rs17849071T/T cases displayed PIK3CA amplification (P = 0.01). Conversely, 1.5% (1/68) cases with PIK3CA amplification vs. 10.4% (33/318) cases without PIK3CA amplification harbored rs17849071G/T (P = 0.01). This provides an explanation for the reciprocal relationship of rs17849071G/T with FTC, since PIK3CA amplification is an important oncogenic mechanism in thyroid cancer, particularly FTC. Thus, the present study uncovers an interesting phenomenon that rs17849071G/T is protective against FTC possibly through preventing PIK3CA amplifications.
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影响因子：
--
作者：
Jiang, Bing-Hua;Liu, Ling-Zhi
通讯作者：
Liu, Ling-Zhi
DOI：
10.1186/bcr1262
发表时间：
2005
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Wu G;Xing M;Mambo E;Huang X;Liu J;Guo Z;Chatterjee A;Goldenberg D;Gollin SM;Sukumar S;Trink B;Sidransky D
通讯作者：
Sidransky D
影响因子：
7
作者：
Collins, FS;Brooks, LD;Chakravarti, A
通讯作者：
Chakravarti, A
影响因子：
5.8
作者：
Liu, Zhi;Hou, Peng;Xing, Mingzhao
通讯作者：
Xing, Mingzhao
影响因子：
3.6
作者：
Bachman, KE;Argani, P;Park, BH
通讯作者：
Park, BH