Phenotypic and genetic profiles of intratumoral heterogeneity in human ovarian cancer

▶ Ovarian tumor was comprised of both phenotypically and genetically distinct subpopulations according to spatial zones.
▶ Phenotypes of SP cells in heterogeneous clones of human ovarian cancer.
▶ Chromosomal alterations in SP cells relative to NSP cells were closely related to the novel core networks of CSCs, such as cycle checkpoint regulation, notch, PTEN, wnt/β-catenin, PI3K/AKT, integrin, and cytokine and chemokine signaling

▶ This study is the first document to define molecular portrait of ITH according to in intratumoral spatial difference. Clones from front zone revealed genetically distinct populations with relatively higher SP proportions, stemness gene expression, frequent chromosomal aberrance by aCGH, and chemotherapeutic resistance. Furthermore, CD24+ cells could be strong potential for tumor progression, drug resistance and clonal asynchronous evolution affecting ITH in consequence. Our evidence for frequent genetic alterations in SP cells compared with NSP cells also suggests that the observed ITH in a single human ovarian cancer tumor specimen could be an effect of clonally diverse evolution from CSCs

Phenotypic and genetic

Characterization of heterogeneous clones generated from different tumor zones. (a) Cell proliferation assays performed at 0, 24, 48, 72, and 96 h after cell seeding confirmed that each clone exhibited a distinctive growth rate and doubling time. (b) Comparison of cell growth property in heterogeneous clones generated from different tumor zones, front and rear, at 96 h. (c) H&E staining was performed to compare differences in morphology at approximately 10 passages. (d) Conventional RT-PCR analyses of the expression of candidate CSC markers. (e) Conventional RT-PCR analyses of the expression of stem cell-related genes. GAPDH was used as an internal control. (f) Cell cycle distribution analysis. All experiments were performed in triplicate. (p<0.05)

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