Grbesa Ivana, Marinkovic Marino, Ivkic Mirko, Kruslin Bozo, Novak-Kujundzic Renata, Pegan Boris, Bogdanovic Ozren, Bedekovic Vladimir, Gall-Troselj Koraljka
Laboratory of Molecular Pathology, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
J Mol Med (Berl). 2008 Sep;86(9):1057-66. doi: 10.1007/s00109-008-0369-4. Epub 2008 Jul 5.
Imprinting analyses of IGF2 and H19, loss of heterozygosity (LOH) analyses of IGF2R and CTCF and Helicobacter pylori detection, were performed on 35 human laryngeal squamous cell carcinomas (LSCC). Forty-six percent of the tumors were heterozygous for IGF2, and 54% were informative for the H19. Biallelic expression of IGF2 was observed in 33% (5 out of 15) of the tumors and in 27% (4 out of 15) of adjacent non-tumorous laryngeal tissues. H19 loss of imprinting (LOI) was observed in 24% (4 out of 17) of the tumors. For IGF2R and CTCF, 71% (25 out of 35) and 50% (17/34), respectively, of the samples were heterozygous, and LOH was detected in 12% (3 out of 25) and 6% (1 out of 17), respectively, of the tumors. H. pylori was found in 26% (9/35) of these tumors. Among them, four were informative for the imprinting analysis. The presence of H. pylori had no effect on IGF2/H19 imprinting. Only the H. pylori detection was further broadened with an additional 47 laryngeal tumors, resulting in a total final positivity of close to 16% (13 out of 82). This study represents the largest comprehensive IGF2/H19 imprinting study done to date on well-defined samples of human laryngeal carcinomas and corresponding non-tumorous tissue. For the first time, the analyses of IGF2/H19 imprinting have been broadened with LOH analyses of IGF2R and CTCF, with both of these genes acting as modulators of IGF2 and H19 activity. Although there were indications that H. pylori may be present in LSCC, we are the first to show its presence in LSCC by two direct techniques: Giemsa staining and nested-PCR.
对35例人喉鳞状细胞癌(LSCC)进行了IGF2和H19的印记分析、IGF2R和CTCF的杂合性缺失(LOH)分析以及幽门螺杆菌检测。46%的肿瘤IGF2为杂合子,54%的肿瘤H19信息丰富。在33%(15例中的5例)的肿瘤和27%(15例中的4例)的相邻非肿瘤性喉组织中观察到IGF2的双等位基因表达。在24%(17例中的4例)的肿瘤中观察到H19印记缺失(LOI)。对于IGF2R和CTCF,分别有71%(35例中的25例)和50%(34例中的17例)的样本为杂合子,在12%(25例中的3例)和6%(17例中的1例)的肿瘤中检测到LOH。在这些肿瘤中,26%(35例中的9例)发现了幽门螺杆菌。其中,4例对印记分析有信息价值。幽门螺杆菌的存在对IGF2/H19印记没有影响。仅对另外47例喉肿瘤进一步扩大了幽门螺杆菌检测,最终总阳性率接近16%(82例中的13例)。本研究是迄今为止对明确的人喉癌样本及相应非肿瘤组织进行的最大规模的综合IGF2/H19印记研究。首次将IGF2/H19印记分析扩展到IGF2R和CTCF的LOH分析,这两个基因均作为IGF2和H19活性的调节因子。尽管有迹象表明LSCC中可能存在幽门螺杆菌,但我们是首次通过两种直接技术(吉姆萨染色和巢式PCR)在LSCC中显示其存在。