Evaluating cell lines as tumor models by comparison of genomic profiles Domcke, S. et al. Nat. Commun 4:2126.

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Presentation transcript:

Evaluating cell lines as tumor models by comparison of genomic profiles Domcke, S. et al. Nat. Commun 4:2126

Motivation  Problem: Genomic differences between cancer cell lines and tissue samples  TCGA and CCLE provide molecular profiles for tumor samples and cell lines  Compared high-grade serous ovarian cancer (HGSOC) to genomic profiles to identify suitable cell lines for in vitro models

Ovarian Cancer  Over 100,000 women die of ovarian cancer each year  5th leading cause of cancer death  Divided into 4 major histological subtypes:  Serous (study’s focus)  Endometrioid  Clear Cell  Mucinous carcinoma

 Common cell line models for ovarian cancer and HGSOC are: SK-OV-3, A2780, OVCAR-3, CAOV3 and IGROV1  Need for well-characterized cell line models for cell types  Found differences between most common models and majority of HGSOC samples

 Analyzed 316 HGSOC tumor samples from TCGA and 47 ovarian cancer cell lines from CCLE  DNA copy-number, mutation and mRNA expression data  Fraction genome altered (FGA): CN=log2(sample intensity/reference intensity) L(i) is length of segment i T is threshold value of Cn i above which segments are altered - T= 0.2 for TCGA samples - T=0.3 for CCLE cell lines

Suitability of HGSOC Models S = A + B – 2×C – D/7 A = Correlation with mean CNA of tumors B = 1 for cell lines with TP53 mutation or else 0 C = 1 for hypermutated cell line or else 0 D = # of genes mutated in 7 “non-HGSOC” genes

Future Directions Drug response profiles using accurate cell line models with known alterations for patient selection in clinical trials Perform preclinical drug screens for more- informed patient therapy Any others?