van Zeeburg Hester J T, Snijders Peter J F, Wu Thijs, Gluckman Eliane, Soulier Jean, Surralles Jordi, Castella Maria, van der Wal Jacqueline E, Wennerberg Johan, Califano Joseph, Velleuer Eunike, Dietrich Ralf, Ebell Wolfram, Bloemena Elisabeth, Joenje Hans, Leemans C René, Brakenhoff Ruud H
Department of Otolaryngology/Head-Neck Surgery, Section Tumor Biology, VU University Medical Center, Amsterdam, the Netherlands.
J Natl Cancer Inst. 2008 Nov 19;100(22):1649-53. doi: 10.1093/jnci/djn366. Epub 2008 Nov 11.
Fanconi anemia is a recessively inherited disease that is characterized by congenital abnormalities, bone marrow failure, and a predisposition to develop cancer, particularly squamous cell carcinomas (SCCs) in the head and neck and anogenital regions. Previous studies of Fanconi anemia SCCs, mainly from US patients, revealed the presence of high-risk human papillomavirus (HPV) DNA in 21 (84%) of 25 tumors analyzed. We examined a panel of 21 SCCs mainly from European Fanconi anemia patients (n = 19 FA patients; 16 head and neck squamous cell carcinomas [HNSCCs], 2 esophageal SCCs, and 3 anogenital SCCs) for their clinical and molecular characteristics, including patterns of allelic loss, TP53 mutations, and the presence of HPV DNA by GP5+/6+ polymerase chain reaction. HPV DNA was detected in only two (10%) of 21 tumors (both anogenital SCCs) but in none of the 16 HNSCCs. Of the 18 tumors analyzed, 10 contained a TP53 mutation. The patterns of allelic loss were comparable to those generally found in sporadic SCCs. Our data show that HPV does not play a major role in squamous cell carcinogenesis in this cohort of Fanconi anemia patients and that the Fanconi anemia SCCs are genetically similar to sporadic SCCs despite having a different etiology.
范可尼贫血是一种隐性遗传性疾病，其特征为先天性异常、骨髓衰竭以及易患癌症，尤其是头颈部和肛门生殖器区域的鳞状细胞癌（SCC）。先前对范可尼贫血相关SCC的研究（主要针对美国患者）显示，在分析的25个肿瘤中有21个（84%）存在高危人乳头瘤病毒（HPV）DNA。我们检测了一组主要来自欧洲范可尼贫血患者的21个SCC（19例范可尼贫血患者；16例头颈部鳞状细胞癌[HNSCC]、2例食管SCC和3例肛门生殖器SCC），分析其临床和分子特征，包括等位基因缺失模式、TP53突变以及通过GP5+/6+聚合酶链反应检测HPV DNA。在21个肿瘤中仅2个（10%）（均为肛门生殖器SCC）检测到HPV DNA，而16例HNSCC中均未检测到。在分析的18个肿瘤中，10个含有TP53突变。等位基因缺失模式与散发性SCC中通常发现的模式相当。我们的数据表明，在这组范可尼贫血患者中，HPV在鳞状细胞癌发生过程中不起主要作用，并且尽管病因不同，但范可尼贫血相关SCC在基因上与散发性SCC相似。
