Loss of heterozygosity, microsatellite instability and TP53 gene status in ovarian carcinomas.
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.


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.


CONCLUSIONS
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.
Department of Molecular Pathology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Joanna
J
Plisiecka-Hałasa
Agnieszka
A
Dansonka-Mieszkowska
Ewa
E
Kraszewska
Anna
A
Dańska-Bidzińska
Jolanta
J
Kupryjańczyk
D002886:Chromosomes, Human, Pair 17; D005260:Female; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D017671:Platinum Compounds / Q000494:pharmacology
D017671:Platinum Compounds