EXPLOITATION OF NEW DIAGNO-THERAPEUTIC PROCEDURES OF HUMAN UTERINE ENDOCERVICAL AND ENDOMETRIAL ADENOCARCINOMAS BASED ON CYTOGENETIC STUDY OF MULTI- STEP CARCINOGENESIS

我们分析了在我院连续手术的宫颈内膜和子宫内膜腺癌患者中TGF βRII、BAX、PTEN/MMAC1基因的突变状态以及微卫星不稳定性（MI）。为了检查携带所有基因的染色体区域的拷贝数损失和/或扩增，我们使用了比较基因组杂交（CGH）分析（传统的和基于阵列的）。CGH分析提供了肿瘤相关基因组失衡的全基因组概述。在宫颈内腺癌中，少数肿瘤表现为MI+表型。此外，PTEN/MMAC1基因在子宫内膜腺癌中表现出明显的氨基酸突变，这在子宫内膜腺癌中尤为突出。CGH分析显示了几个有希望的癌基因，它们可能在子宫内膜癌和子宫内膜腺癌的多步骤癌变中起作用。子宫内膜癌和宫颈内腺癌多步骤癌变的细胞遗传学机制有待进一步研究。

We analyzed the mutational status of the TGF βRII, BAX, and PTEN/MMAC1 genes as well as microsatellite instability (MI) in consecutive cases of endocervical and endometrial adenocarcinomas of the uterus operated on at our Institute. To examine copy number losses and/or amplifications at the chromosomal region bearing all the genes, we used comparative genomic hybridization (CGH) analysis (both conventional and array-based). CGH analysis provides a genome-wide overview about tumor-associated genomic imbalances. Among the tumors, a few showed the MI+ phenotype in endocervical adenocarcinoma. Also, few tumors demonstrated a significant mutation with a definite amino acid change in PTEN/MMAC1 gene, which is prominent in endometrial adenocarcinoma. CGH analysis demonstrated several promising oncogenes which may have a role in multi-step carcinogenesis of uterine endocervical and endometrial adenocarcinomas.Additional explorations are needed to elucidate the cytogenetic mechanisms of multi- step carcinogenesis in endocervical and endometrial adenocarcinomas of the uterus.