Cumulative dosage effect of a RAD51L1/HMGA2 fusion and RAD51L1 loss in a case of pseudo-Meigs' syndrome.
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.
Amant
F
F
Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium. Frederic.Amant@uz.kuleuven.be
Debiec-Rychter
M
M
Schoenmakers
E F
EF
Hagemeijer-Hausman
A
A
Vergote
I
I
D000328:Adult; D002455:Cell Division / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D018628:Gene Dosage; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007889:Leiomyoma / Q000235:genetics* / Q000473:pathology; D008539:Meigs Syndrome / Q000235:genetics* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D051135:Rad51 Recombinase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
D004268:DNA-Binding Proteins; D025743:HMGA2 Protein; D015514:Oncogene Proteins, Fusion; C495153:RAD51 protein, human; D051135:Rad51 Recombinase