Uterine leiomyoma cytogenetics

Abstract

Uterine leiomyoma--a benign smooth muscle tumor--has recently been found to contain tumor-specific chromosome aberrations. Although only normal karyotypes were detected in 50 to 80% of cytogenetically investigated tumors, 104 leiomyomas with karyotypic aberrations have already been reported. At least four cytogenetically abnormal subgroups have been identified thus far, characterized by rearrangements of 6p, del(7)(q21.2q31.2), +12, and t(12;14)(q14-15;q23-24). The remaining abnormal tumors have had various nonrecurrent anomalies. Secondary karyotypic rearrangements, sometimes including ring chromosomes, have been found in one-third and reflect clonal evolution. Occasional leiomyomas have contained multiple numerical and structural rearrangements. Though benign, these cytogenetically grossly aberrant tumors often displayed more atypical histological features than are usually seen in leiomyoma. Multiple leiomyomas have been investigated from 69 patients, with detection of chromosome anomalies in at least two separate tumors from the same uterus in ten cases. In half of these patients unrelated aberrations were found in different leiomyomas from the same uterus. On other occasions the aberrations were identical, indicating that although some uterine leiomyomas originate independently, others may develop by intra-myometrial spreading from a common neoplastic clone. Some common features are discernible between the karyotypic pictures of uterine leiomyoma and angioleiomyoma; rearrangements of 6p, 13q, and 21q have been described in both tumor types. The cytogenetic similarities so far detected between leiomyoma and the malignant muscle tumors--leiomyosarcoma and rhabdomyosarcoma--are few and may be fortuitous. The cytogenetic profiles of leiomyoma and lipoma are strikingly similar; both tumor types have nonrandom rearrangements of 12q13-15, t(12;14) in leiomyoma and t(3;12) in lipoma, as well as variant rearrangements of the same 12q segment. Both also have cytogenetic subgroups characterized by changes in 6p and ring chromosomes. Finally, karyotypic similarities exists also between leiomyoma and pleomorphic adenoma of the salivary gland, which includes a subset of tumors with anomalies of 12q13-15, and with myxoid liposarcoma, which has t(12;16)(q13;p11) as a tumor-specific rearrangement.

Loss of the repressor REST in uterine fibroids promotes aberrant G protein-coupled receptor 10 expression and activates mammalian target of rapamycin pathway

“…Loss of REST is known to result in mitotic arrest deficient-like 1 (MAD2)-mediated genomic instability in tumor-derived cell lines (45). Recurring chromosomal translocations and gene mutations have also been shown to exist in uterine fibroids (46).…”

Etiology and pathogenesis of uterine leiomyomas: a review.

“…There have been numerous studies and reviews of the clonality and cytogenetics of uterine leiomyomas (Gross and Morton 2001;Ligon andMorton 2000, 2001;Mark et al 1988;Nilbert and Heim 1990;Ozisik et al 1993b;Pandis et al 1991). For the purposes of this brief review, we have attempted to summarize those features that appear most salient.…”

“…In some series del(7q) has been the most common cytogenetic abnormality in fibroids (Nilbert and Heim 1990;Ozisik et al 1993b). Although interstitial deletions and translocations involving chromosome 7q have also been reported in other benign tumors, such as lipomas and endometrial polyps, the deletion is more commonly observed in fibroids than in any other solid tumor.…”

Expression profile of tuberin and some potential tumorigenic factors in 60 patients with uterine leiomyomata

“…2 Nonrandom chromosomal abnormalities are found in up to 40% of leiomyomata. 3,4 The high-mobility group protein genes are considered candidate genes for leiomyomata as these were identified from breakpoints of chromosomal translocation in leiomyomata. 3,5 Although an upregulation of high-mobility group protein gene A2 has been found in some leiomyomata, 5,6 the fusion highmobility group protein gene A2 by truncated transcripts at translocation breakpoints is not a common molecular event.…”