ABSTRACT
Uterine leiomyoma presenting with ascites and pleural fluid is referred to as pseudo-Meigs' syndrome. It is unclear whether common uterine leiomyomas and uterine leiomyomas causing pseudo-Meigs' syndrome are cytogenetically related or whether functionally different primary pathogenetic triggers are responsible for the differences in tumor phenotype. In this study, we investigated the possible involvement of RAD51LI and HMGA2 (formerly known as HMGIC) in initiation and/or progression of a huge uterine leiomyoma presenting as pseudo-Meigs' syndrome. The detailed cytogenetic and FISH analysis revealed the presence of two subclones with a complex karyotype, 46,XX,t(2;12)(q31;q21),ins(14;12)(q23-24;q15q21).ish del(12)(q15q15) (LL12NC01-142H1-,LL12NC01-27E12-),der(12)t(2;12)(LL12NC01-142H1+,LL12NC01-27E12-),der(14)ins(14;12)(q22;q15q15) (LL12NC01-142H1+,LL12NC01-27E12+,RAD51LI+), der(14)ins(14;12)(q23-q24;q15q21) (LL12NC01-142H1-, LL12NC01-27E12+) [20]/46,idem,del(14)(q21q24).ish(RAD51LI-) [6], indicating intragenic HMGA2 rearrangement and loss of one of the RAD51LI alleles in a derivative subclone with chromosome 14 deletion. Furthermore, RACE and RT-PCR analysis of the tumor cells did not reveal abnormal HMGA2 or RAD51LI transcripts. Additionally, the cellular subclone with intrachromosomal 14q21-q24/RAD51LI deletion showed an in vitro growth advantage over the subclone without the deletion. This observation supports a model in which accumulation of two independent mutations-a classical structural rearrangement involving HMGA2 and RAD51L1, in combination with a loss of the second RAD51L1 allele-might play a major role in the development of pseudo-Meigs' syndrome.
Subject(s)
DNA-Binding Proteins/genetics , Gene Deletion , Gene Dosage , HMGA2 Protein/genetics , Leiomyoma/genetics , Meigs Syndrome/genetics , Oncogene Proteins, Fusion/genetics , Uterine Neoplasms/genetics , Adult , Cell Division/genetics , Female , Gene Amplification , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Leiomyoma/pathology , Meigs Syndrome/pathology , Rad51 Recombinase , Reverse Transcriptase Polymerase Chain Reaction , Uterine Neoplasms/pathologyABSTRACT
Uveal melanoma is the most common primary intraocular tumor in adults in the western world. Recent studies indicate that the presence of cytogenetic abnormalities in tumor cells is strongly linked with prognosis. The purpose of this project is the detection of chromosomal abnormalities in a series of frozen tumors (retrospective study) and of fresh tumor tissues (prospective study) and to correlate these results with other prognostic factors and survival.
