Loss of Heterozygosity, Microsatellite Instability and TP53 Gene Status in Ovarian Carcinomas

• Published in: Anticancer research Vol. 28; no. 2A; pp. 989 - 996
• Main Authors: JOANNA PLISIECKA-HALASA, AGNIESZKA DANSONKA-MIESZKOWSKA, EWA KRASZEWSKA, ANNA DAŃSKA-BIDZIŃSKA, JOLANTA KUPRYJAŃCZYK
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-03-2008
• Subjects: Biological and medical sciences; Chromosomes, Human, Pair 17; Female; Female genital diseases; Genes, p53; Gynecology. Andrology. Obstetrics; Humans; Loss of Heterozygosity; Medical sciences; Microsatellite Instability; Microsatellite Repeats; Mutation; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Platinum Compounds - pharmacology; Tumors; Rb protein; Ovary carcinoma; Allelic imbalance; Retinoblastoma gene; Ovary cancer; ovarian carcinoma; Malignant tumor; Female genital diseases; RB; Ovarian diseases; Chemotherapy; Treatment; Cancerology; TP53 Gene; Microsatellite DNA; Loss of heterozygosity; Instability; TP53; Cancer; Tumor suppressor gene
• ISSN: 0250-7005; 1791-7530

Background: 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. Materials and Methods:
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. Results: 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. Conclusion: 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.