Allelotype of uterine leiomyomas ; Deletion of chromosomal region 7q21-31

Park, T C; Shin, J C; Kim, C J; Kwon, Y I; Kim, H K; Um, S J; Lee, J M; Namkoong, S E; Park, J S

Abstract

OBJECTIVE
Uterine leiomyoma is benign smooth muscle tumor of the myometrium and is the most common uterine neoplasm, occurring in about 30% of women over 30 years of reproductive age. Although uterine leiomyoma is an endocrine dependent tumor whose size and growth is influenced by estrogen and progesterone, its etiology is unknown. As for benign tumor, the pathogenesis of leiomyoma remains obscure, especially at the molecular genetic level. Cytogenetic studies have identified several nonrandom chromosomal alterations that occur frequently in this tumor, and are presumably involved in its etiology. To determine which chromosomal regions contain what is called tumor growth suppressor genes important for human uterine leiomyoma, we performed loss of heterozygosity[LOH] studies in all chromosome and to further defined the small region of common loss of chromosome 7q which the fore part detected, we used highly microsatellite markers spanning no more than 70 cM, located between 7q21 and 7q31, to examined allelic loss.
METHODS
Sixty-eight highly informative polymorphic microsatellite markers, distributed to arms of autosomal chromosomes in 42 uterine leiomyomas, were examined for evidence of LOH or allelic imbalance in DNA samples. And the 7q21-31 region with 17 polymorphic microsatellite markers were examined for evidence of LOH or allelic imbalance in 32 pairs of extracted DNAs from matched normal myometriums and leiomyoma tissues.
RESULTS
Allelic deletion or imbalance were observed on 33 of 41 chromosome arms and those chromosome arms frequently involved were 3q[19.4%], 5[p:17.2%, q:20.7%], 6[p:23.3%, q:23.7%], 7q[30.5%], 9q[22.9%], 12[p:24.1%, q:22.7%], 14q[18.5%] and Xp[18.5%], and then particularly 30.5% of LOH of chromosome 7q highly detected of them. Thirty-two tumors were examined for allelic loss of loci between D7S440 and D7S684 on the 7q11-31 region. LOH for one or more of these loci was observed in 56.9% of the tumors at the markers D7S477, D7S518, D7S666, D7S515, D7S501 and D7S496 on the 7q 21-22 region.
CONCLUSION
Our results further define a region that is accordantly lost in leiomyoma with molecular-genetic deletion of chromosome 7q showed that high percentage of LOH is located at 7q21-22 region and suggested that tumor suppressor gene involved in the development of a subset of uterine leiomyoma.