Search

Aberrations of the HMGIC gene, encoding an architectural transcription factor and located in the chromosomal region 12q15, are very frequent among benign mesenchymal tumors, such as lipomas, uterine leiomyomas, or pulmonary chondroid hamartomas. These HMGIC aberrations are caused by characteristic structural chromosomal aberrations, either visible by conventional cytogenetics or as cryptic abnormalities. Some of these aberrations of chromosome 12 are not specific for particular tumor entities but can occur in a variety of tumors with HMGIC abnormalities. One such example is the pericentric inversion inv(12)(p11.2q15). Starting from the ectopic sequence derived from an HMGIC fusion transcript of an aggressive angiomyxoma with such an inversion we established three PAC clones covering the breakpoint region 12p11 and cloned part of a yet unknown gene in 12p11.2, which is fused to the third exon of HMGIC. Using fluorescence in situ hybridization with these PACs we were able to show that the same region was involved by 12p11.2 aberrations in lipomas, aggressive angiomyxomas, and pulmonary chondroid hamartomas.

Aggressive angiomyxoma is a rare mesenchymal tumor occurring mainly in the vulvar region extending into the paravaginal and perirectal region. Histologically, this tumor is rich in vascular structures and in collagen fibers and is of myxoid appearance. Cytogenetic and molecular analysis was performed on a case of an aggressive angiomyxoma and revealed clonal karyotypic abnormalities. All 50 metaphases analyzed showed a translocation involving the chromosomal region 12q14-15. Chromosomal aberrations involving the breakpoint region 12q14-15 are frequently seen in a variety of other mesenchymal tumors as uterine leiomyomas, lipomas, hamartomas of the lung, liposarcomas, or hemangiopericytomas. Therefore, this breakpoint region seems to be the most frequent chromosomal abnormality associated with the initiation of human mesenchymal neoplasms. To narrow down the breakpoint region on a molecular level in the cells of the angiomyxoma we performed FISH analysis with different cosmid clones originating from a yeast artificial chromosome and cosmid contig overspanning parts of the region 12q14-15. We were able to narrow down the region to approximately 70-80 kb belonging to an area designated a multiple aberration region, because it also includes the breakpoints of leiomyomas, lipomas, and pleomorphic adenomas with 12q13-15 abnormalities. Our molecular and cytogenic data suggest that angiomyxomas or at least a subset of them molecularly belong to the benign group of mesenchymal tumors showing multiple aberration region involvement.