Human papillomavirus-16 and -18 in penile carcinomas: DNA methylation, chromosomal recombination and genomic variation.
Human papillomavirus-16 and -18 in penile carcinomas: DNA methylation, chromosomal recombination and genomic variation.
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DOI：
10.1002/ijc.23707
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发表时间：
2008-10-15
影响因子：
6.4
通讯作者：
Bernard, Hans-Ulrich
中科院分区：
文献类型：
--
作者：
Kalantari, Mina;Villa, Luisa L.;Calleja-Macias, Itzel E.;Bernard, Hans-Ulrich
阴茎癌通常与高危型人乳头瘤病毒（HPV）有关。由于对这种关联的分子生物学知之甚少，我们研究了巴西患者阴茎癌中HPV基因组的三个特性：（i）HPV DNA甲基化，（ii）HPV与细胞DNA之间的连接，以及（iii）基因组变异。在宫颈癌发生中，HPV和染色体DNA之间的重组是频繁的，并且可能是进展所必需的，DNA超甲基化-特别是L1基因-是癌进展的生物标志物。在阴茎癌的发生过程中也存在同样的机制，因为来自19个阴茎病变的95个HPV-16分子中，L1区58%的CpG和长对照区5′部分22%的CpG发生甲基化，高于宫颈癌中发现的百分比。此外，三分之二的HPV-18感染（均存在于HPV-16双重感染中）显示出典型的恶性宫颈病变的L1特异性甲基化。在15个HPV-16病变中的11个中，我们通过反向连接反向PCR证实了染色体整合，而4个样品具有多联体整合或附加体。17例阴茎癌中有9例含有HPV-16 AA变异体，8例含有E变异体。由于AA变异体在巴西无症状女性队列中相对罕见，阴茎癌的高患病率可能表明AA病变进展的风险较高，怀疑是宫颈感染。我们对频繁的病毒DNA甲基化、染色体整合和高危变异的流行的观察表明，HPV依赖的阴茎和宫颈癌发生遵循相似的病因学和流行病学参数。
Penile carcinomas are frequently associated with high-risk human papillomavirus (HPV) types. Since little is known about the molecular biology of this association, we investigated three properties of HPV genomes in penile carcinomas from Brazilian patients: (i) HPV DNA methylation, (ii) junctions between HPV and cellular DNA, and (iii) genomic variation. In cervical carcinogenesis, recombination between HPV and chromosomal DNA is frequent and likely necessary for progression, and DNA hypermethylation - specifically of the L1 gene - is a biomarker for cancerous progression. The same mechanisms apparently occur during penile carcinogenesis, because 95 HPV-16 molecules derived from 19 penile lesions had 58% of the CpGs in L1 and 22% in the 5′ part of the long control region methylated, more than the percentages found in cervical carcinomas. In addition, two out of three HPV-18 infections, all present in double-infections with HPV-16, showed L1 specific methylation typical of malignant cervical lesions. In 11 out of 15 HPV-16 lesions we confirmed chromosomal integration by reverse ligation inverted PCR, while four samples had concatemeric integrations or episomes. Nine of 17 penile carcinomas contained HPV-16 AA variants, and eight E variants. As AA variants are relatively rare in Brazilian cohorts of asymptomatic women, the high prevalence in penile carcinomas may indicate a higher risk of progression of AA lesions, as suspected for cervical infections. Our observations of frequent viral DNA methylation, chromosomal integration, and the prevalence of high-risk variants suggest that HPV dependent carcinogenesis of the penis and cervix follow similar etiological and epidemiological parameters.
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影响因子：
3.7
作者：
Bhattacharjee, Bornali;Sengupta, Sharmila
通讯作者：
Sengupta, Sharmila
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