Parallel karyotypic evolution and tumor progression in uterine leiomyoma

Abstract

Cytogenetic evidence of clonal evolution was detected in five uterine leiomyomas. In two tumors, two clones were found, the third tumor had four, the fourth had nine, and the fifth had 12 clones. The first tumor had trisomy 12 as the primary anomaly and a sideline that also contained a del(7)(q21q31). Both clones of the second tumor had three structural changes in common but differed by the presence in the more advanced clone of an inv(7)(q31q34). Two cytogenetically unrelated pairs of clones were seen in the third tumor. One clone had a stemline of 46 and an r(1); a sideline had developed through duplication of this clone. The other pair had a del(7)(q21q31) in common. The last two tumors both had t(12;14)(q14-15;q23-24) as the primary abnormality. They also had a high frequency of telomeric associations that involved certain chromosome arms only. One of the secondary changes in the fourth tumor was a del(7)(q21q31); the principal secondary change in the fifth case was a ring chromosome 1 of variable size in the different clones. The analysis of these five uterine leiomyomas and the collation of the results with previously obtained data lead us to conclude that del(7)(q21q31) is secondary to t(12;14) and + 12 in this tumor type, and that ring formation involving chromosome 1 material, often with duplication of segments, is a common phenomenon during clonal evolution. The fact that the tumors were classified as cellular and had an increased mitotic rate indicates a parallel development between histologically detectable tumor progression and cytogenetically recognizable clonal evolution in uterine leiomyomas.

Analysis of androgen receptor DNA reveals the independent clonal origins of uterine leiomyomata and the secondary nature of cytogenetic aberrations in the development of leiomyomata

“…Karyotypic evolution has been noted previously in uterine leiomyomata (Pandis et al, 1990). In some tumors, cells with differing karyotypes had a primary abnormality in common, whereas in others entirely different cytogenetic abnormalities were noted within cells cultured from the same tumor.…”

Etiology and pathogenesis of uterine leiomyomas: a review.

“…Environmental Health Perspectives • VOLUME 111 | NUMBER 8 | June 2003 found in one study (Nilbert and Heim 1990); however, there is some evidence from other reports (Meloni et al 1992;Pandis et al 1990) that leiomyomas that are either cellular with mitotic activity or atypical histologically are more likely to demonstrate karyotypic abnormalities or to show massive karyotypic aberrations indicative of clonal evolution. In a study of 114 myomas from 92 patients, myomas > 6.5 cm demonstrated a significantly higher proportion of abnormal karyotypes than myomas < 6.5 cm (75% vs. 34%) (Rein et al 1998).…”

“…Taken in sum, however, the concept of monoclonal origin of most fibroids appears to be a valid one, recognizing that some could be biclonal in origin (Ozisik et al 1993a) and some are biclonal or oligoclonal because of clonal evolution (Pandis et al 1990), and that monoclonality itself could be the result of selective overgrowth of one clone from an originally polyclonal proliferation (Fey et al 1992;Vogelstein et al 1987).…”

Loss of heterozygosity and reduced expression of the CUTL1 gene in uterine leiomyomas

“…The most frequent genetic alteration, del(7q), was found in approximately 35% of studied cases with cytogenetic abnormalities (128/366), and the smallest commonly deleted region of 7q was mapped to band 7q22 (Ozisik et al, 1993b;Sargent et al, 1994). Deletion of 7q22 was also found in a small proportion of primary AML (7.6%) and MDS (19%), however, its incidence increased to 26.8 and 41% respectively in secondary AML and MDS (Litt et al, 1993;Pandis et al, 1990Pandis et al, , 1991. The high proportion of cytogenetically detectable deletions of 7q22 in dierent cancers suggests that a tumor suppressor gene may be located within this chromosomal region (Ozisik et al, 1993b;Yunis et al, 1988a).…”