Chromosomal copy number and mutational status are required to authenticate ovarian cancer cell lines as appropriate cell models

TL;DR

This study shows that ovarian cancer cell line IGROV-1 has inconsistent genetic profiles, suggesting the need for better authentication methods.

Contribution

The study introduces the need for chromosomal copy number and mutational status analysis alongside STR fingerprinting for cell line authentication.

Findings

IGROV-1-NKI and IGROV-1-MDA have different chromosomal profiles and low STR match between them.

IGROV-1-MDA is more resistant to cisplatin and olaparib than IGROV-1-NKI.

IGROV-1 has a mutational profile consistent with both Type I and Type II ovarian cancer.

Abstract

The mutational status of ovarian cancer cell line IGROV-1 is inconsistent across the literature, suggestive of multiple clonal populations of the cell line. IGROV-1 has previously been categorised as an inappropriate model for high-grade serous ovarian cancer.

IGROV-1 cells were obtained from the Netherlands Cancer Institute (IGROV-1-NKI) and the MD Anderson Cancer Centre (IGROV-1-MDA). Cell lines were STR fingerprinted and had their chromosomal copy number analysed and BRCA1/2 genes sequenced. Mutation status of ovarian cancer-related genes were extracted from the literature.

The IGROV-1-NKI cell line has a tetraploid chromosomal profile. In contrast, the IGROV-1-MDA cell line has pseudo-normal chromosomes. The IGROV-1-NKI and IGROV-MDA are both STR matches (80.7% and 84.6%) to the original IGROV-1 cells isolated in 1985. However, IGROV-1-NKI and IGROV-1-MDA are not an STR match to each other (78.1%) indicating genetic drift. The BRCA1 and BRCA2 gene sequences are 100% identical between IGROV-1-MDA and IGROV-1-NKI, including a BRCA1 heterozygous deleterious mutation. The IGROV-1-MDA cells are more resistant to cisplatin and olaparib than IGROV-1-NKI. IGROV-1 has a mutational profile consistent with both Type I (PTEN, PIK3CA and ARID1A) and Type II ovarian cancer (BRCA1, TP53) and is likely to be a Type II high-grade serous carcinoma of the SET (Solid, pseudo-Endometroid and Transitional cell carcinoma-like morphology) subtype.

Routine testing of chromosomal copy number as well as the mutational status of ovarian cancer related genes should become the new standard alongside STR fingerprinting to ensure that ovarian cancer cell lines are appropriate models.

The online version contains supplementary material available at 10.1007/s11033-024-09747-4.

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