Molecular and cytogenetic analysis of chromosome 7 in uterine leiomyomas

Abstract

Uterine leiomyomas are benign tumors that arise clonally from smooth muscle cells of the myometrium. Cytogenetic studies of uterine leiomyomas have shown that about 40% have chromosome abnormalities and that deletion of 7q is a common finding. The observations suggest the possible location of a growth-suppressor gene within the 7q21-q22 region. Molecular genetic analysis of cytogenetically normal tumors has frequently shown somatic loss of specific tumor suppressor genes detected by loss of heterozygosity in the critical region. To test the hypothesis that chromosome region 7q21-q22 contains a growth-suppressor gene involved in the development of leiomyomas, we examined 92 leiomyomas for allelic loss of 7q markers spanning the cytogenetically defined critical region. Forty tumors with cytogenetically defined 7q deletion, 45 tumors without cytogenetically visible 7q deletion, and seven tumors with no cytogenetic information were examined for allelic loss of loci D7S489, D7S440, D7S492, D7S518, D7S471, D7S466, and D7S530. Loss of heterozygosity for one or more of these loci was observed in 23 of 40 (57.5%) of the tumors with deletion of 7q and in 2 of 45 cases without a cytogenetically visible deletion. The tumors with cytogenetic deletion of 7q, but no loss of 7q21-q22 markers, were mosaics, with only a minority of cells containing the cytogenetic deletion. The critical region of loss is defined by the markers D7S518 and D7S471, each showing loss in approximately 50% of informative cases.(ABSTRACT TRUNCATED AT 250 WORDS)

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

“…These results are in agreement with the study of Ishwad et al (1995), in which the smallest common deleted region was mapped between markers D7S471 and D7S518 (Ishwad et al, 1995). Moreover, the LOH frequency of polymorphic markers as determined in these two studies agreed well with the frequency of chromosomal deletion in cytogenetic studies (17%).…”

“…Moreover, the LOH frequency of polymorphic markers as determined in these two studies agreed well with the frequency of chromosomal deletion in cytogenetic studies (17%). However, Ishwad et al noted that approximately 40% (17 of 40) of the tumors with cytogenetically de®ned 7q deletions had no LOH for markers in this chromosomal region (Ishwad et al, 1995). Two explanations were provided by the authors to explain the lack of allelic loss in many tumors with cytogenetically visible 7q deletion.…”

7q deletion mapping and expression profiling in uterine fibroids

“…Also, the lack of chromosomal deletions in two tumours showing LOH indicates that mitotic recombination, rather than deletion, may be the cause of LOH in some fibroids (Gupta et al, 1997;Blackburn et al, 2004). Since the previous deletion mapping efforts on fibroids were conducted before the final version of the human genetic map was available, some of the marker information has changed (Ishwad et al, 1995(Ishwad et al, , 1997van der Heijden et al, 1998;Mao et al, 1999). In particular, the results by van der Heijden et al rely critically on marker D7S501, the published reverse primer of which does not have a perfect match on the 7q22.3 target region in the latest version (v29.35b) of Ensembl (www.ensembl.org) genome browser, thus making the assessment of LOH in our experience nonreproducible (data not shown).…”

“…The most common alterations have been deletions on chromosome 7q21-q31, and other abnormalities have involved chromosomes 6, 12 and 14 (Nibert and Heim, 1990). In addition, several allelotyping studies of uterine fibroids have discovered deletions on chromosome 7q21-q31 (Ishwad et al, 1995(Ishwad et al, , 1997van der Heijden et al, 1998;Mao et al, 1999). All these studies consistently point to a common deleted region around markers D7S518 and D7S471, which according to Knudson's two-hit model suggests a leiomyoma suppressor gene in that region.…”

Expression of N‐terminally truncated isoforms of CDP/CUX is increased in human uterine leiomyomas

“…5 Deletions on chromosome 7q, del(7q), were found in approximately 35% of cases with cytogenetic abnormalities (128/ 366), and the smallest commonly deleted region of 7q was mapped to band 7q22. 1,[7][8][9][10] The high proportion of cytogenetically detectable deletions of 7q22 in leiomyomas and other types of cancer suggests that a tumor-suppressor gene may be located within this chromosomal region. 1,9 We previously reported that CUTL1 was present in a commonly deleted region in 7/50 uterine leiomyoma samples examined.…”