Plisiecka-Hałasa Joanna, Dansonka-Mieszkowska Agnieszka, Kraszewska Ewa, Dańska-Bidzińska Anna, Kupryjańczyk Jolanta
Department of Molecular Pathology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Anticancer Res. 2008 Mar-Apr;28(2A):989-96.
Microsatellite instability (MSI) and loss of heterozygosity (LOH) are frequent events in ovarian carcinogenesis; however, little is known as to their clinical significance and association with other molecular lesions.
Twelve microsatellite markers for MSI and LOH analysis were used in 64 ovarian carcinomas with known TP53 mutational status. The clinical importance of molecular alterations was evaluated in a uniform subgroup of patients treated with platinum-based regimens.
LOH was detected in order of frequency at 17p13.3 (D17S926, 79%), 17p13.1 (TP53 locus, 69%), 13q14 (RB, 60%), 3p21 (D3S1611, 32.5%), 8q21 (D8S1811, 22%), 11p14/13 (D11S904, 19%), 10qter (D10S197, 13%) and 2p16-21 (D2S123, 11%). LOH at the RB1 locus showed association with LOH at the TP53 locus (p = 0.01). Platinum sensitivity was associated with heterozygosity at the TP53 locus (p = 0.006). Only one tumor displayed microsatellite instability in one marker (RB) only.
Our results suggest that LOH at the 17p D17S926 locus in ovarian cancer is an earlier molecular event than LOH at the TP53 locus. Inactivation of TP53 and RB1 genes may have a synergistic effect in ovarian tumorigenesis.
微卫星不稳定性（MSI）和杂合性缺失（LOH）是卵巢癌发生过程中的常见事件；然而，关于它们的临床意义以及与其他分子病变的关联却知之甚少。
采用12个用于MSI和LOH分析的微卫星标记，对64例已知TP53突变状态的卵巢癌进行检测。在接受铂类方案治疗的患者统一亚组中评估分子改变的临床重要性。
按频率依次检测到LOH的位点为17p13.3（D17S926，79%）、17p13.1（TP53位点，69%）、13q14（RB，60%）、3p21（D3S1611，32.5%）、8q21（D8S1811，22%）、11p14/13（D11S904，19%）、10qter（D10S197，13%）和2p16 - 21（D2S123，11%）。RB1位点的LOH与TP53位点的LOH相关（p = 0.01）。铂敏感性与TP53位点的杂合性相关（p = 0.006）。仅1例肿瘤仅在一个标记（RB）中显示微卫星不稳定性。
我们的结果表明，卵巢癌中17p D17S926位点的LOH是比TP53位点的LOH更早发生的分子事件。TP53和RB1基因的失活在卵巢肿瘤发生过程中可能具有协同作用。
