Department of Cancer Genome Research, Sasaki Institute, Sasaki FoundationAbstract公益財団法人佐々木研究所附属佐々木研究所腫瘍ゲノム研究部― 159 ―In the 1950th, Slaughter and colleagues introduced the concept of field cancerization that a large contiguous field with genetic alterations is present in histologically normal tissues and multiple clonally related neoplastic lesions develop from the field. Although several lines of evidence support the field cancerization model in many types of cancers, the field from which endometriosis-associated ovarian cancers including ovarian clear cell carcinoma and endometrioid carcinoma remains elusive. Recently, we demonstrated that somatic mutations in cancer-associated genes accumulated in the normal human endometrial epithelium with aging and cumulative number of menstrual cycles. We discovered network-like glandular structures that run horizontally along the muscle layer at the bottom of the endometrium. We named this structure as rhizome structure. In addition, we showed that endometrial glands connected through rhizome structure shared somatic mutations, indicating that rhizome structure is involved in spatial expansion of mutant clones in the normal endometrium. This finding implies that normal endometrium remodeled by mutant clones that are expanded through rhizome structure could be the field in which ancestral mutant clone of endometriosis and endometriosis-associated ovarian cancer emerges. As the initial step, we examined functional characterization of rhizome structure by performing a transcriptome analysis, in which epithelial and stromal cells were selectively collected by laser-microdissection from each of three layers of uterine endometrium (the luminal surface, the stratum functionalis and the stratum basalis [or rhizome structure]). Epithelial cells of rhizome structure showed significant increased expressions of stem/progenitor cell markers and genes that were involved in Wnt signaling pathway. The result suggests that rhizome structure may contain cells which function as a niche of endometrial epithelial stem/progenitor cells and contribute to expansion, homeostasis, and repair of endometrial epithelial cells during menstrual cycle. There Field cancerization of endometriosis-associated 子宮内膜症関連卵巣がんの起源となるfield cancerizationの探索ovarian cancer中岡 博史Hirofumi Nakaoka
元のページ ../index.html#161