MOLECULAR AND CYTOGENETIC ANALYSIS OF CHROMOSOME-7 IN UTERINE LEIOMYOMAS

Uterine leiomyomas are benign tumors that arise clonally from smooth m uscle cells of the myometrium. Cytogenetic studies of uterine leiomyom as have shown that about 40% have chromosome abnormalities and that de letion of 7q is a common finding. The observations suggest the possibl e location of a growth-suppressor gene within the 7q21-q22 region. Mol ecular genetic analysis of cytogenetically normal tumors has frequentl y shown somatic loss of specific tumor suppressor genes detected by lo ss of heterozygosity in the critical region. To test the hypothesis th at chromosome region 7q21-q22 contains a growth-suppressor gene involv ed in the development of leiomyomas, we examined 92 leiomyomas for all elic loss of 7q markers spanning the cytogenetically defined critical region. Forty tumors with cytogenetically defined 7q deletion, 45 tumo rs without cytogenetically visible 7q deletion, and seven tumors with no cytogenetic information were examined for allelic loss of loci D7S4 89, D7S440, D7S492, D7S518, D7S471, D7S466, and D7S530. Loss of hetero zygosity 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 cyt ogenetically visible deletion. The tumors with cytogenetic deletion of 7q, but no loss of 7q21-q22 markers, were mosaics, with only a minori ty of cells containing the cytogenetic deletion. The critical region o f loss is defined by the markers D7S518 and D7S471, each showing loss in approximately 50% of informative cases. These markers define a 10 c M region of 7q21-q22 that is consistent with the cytogenetically defin ed smallest region of overlap and exclude loss of the MET oncogene loc us and WNTI, the murine mammary tumor-virus integration site, from the critical region. Our results further define a region that is consiste ntly lost in leiomyomas with cytogenetic deletion of chromosome arm 7q . This region may contain a tumor suppressor gene involved in the deve lopment of a subset of leiomyomas. (C) 1995 Wiley-Liss, Inc.