ABSTRACT: Little is known about a relationship between intratumor heterogeneity and drug resistant ability in high grade serous ovarian cancer. Using stem cell cloning technique on high grade ovarian cancer, we have cloned ovarian cancer colonies at high efficiency. The heterogeneity of ovarian cancer is recapitulated in cloned cancer colony library, and Taxol treatment (100 nM 3 hrs) has been conducted on cancer library and obtained drug resistant cancer clones in vitro. Using cloned original cancer colonies and drug resistant cancer colonies, we have studied the effect of intratumor heterogeneity on acquisition of drug resistance. Overall design: We have used surgery samples of high grade serous ovarian cancer and cultured cancer cell colony on 3T3 feeder layer. We used Affymetrix human exon 1.0 st array chip to hybridize 2 samples from each of drug treatments and clones. 100 nM 3hrs Taxol treatment was done 1st round (G1), 2nd round (G2) and 3rd round (G3). Cancer colonies (N1, N3, N7, N9, N10, N11, N25, N39, N41, N42, N43, N49, N50, N56, N58, N61, N62, N69, N75, N78, N81, N82, N94) were cloned from original pooled culture of ovarian cancer cells. Drug resistant cancer colonies (R3, R5, R20, R33, R90, R91, R92, R94 and R95) were cloned from Taxol-treated (four times) ovarian cancer cells (pooled).
Frank McKeon