Genomic Characterization of Preclinical Prostate Cancer Cell Line Models

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jun 19

PMID 38892296

Authors

Erica L Beatson

Emily N Risdon

Giulia C Napoli

Douglas K Price

Cindy H Chau

William D Figg

Affiliations

Soon will be listed here.

Abstract

As we move into the era of precision medicine, the growing relevance of genetic alterations to prostate cancer (PCa) development and treatment demonstrates the importance of characterizing preclinical models at the genomic level. Our study investigated the genomic characterization of eight PCa cell lines to understand which models are clinically relevant. We designed a custom AmpliSeq DNA gene panel that encompassed key molecular pathways targeting AR signaling, apoptosis, DNA damage repair, and PI3K/AKT/PTEN, in addition to tumor suppressor genes. We examined the relationship between cell line genomic alterations and therapeutic response. In addition, using DepMap's Celligner tool, we identified which preclinical models are most representative of specific prostate cancer patient populations on cBioPortal. These data will help investigators understand the genetic differences in preclinical models of PCa and determine which ones are relevant for use in their translational research.

References

Ng P, Henikoff S . SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003; 31(13):3812-4. PMC: 168916. DOI: 10.1093/nar/gkg509. View

Taylor B, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver B . Integrative genomic profiling of human prostate cancer. Cancer Cell. 2010; 18(1):11-22. PMC: 3198787. DOI: 10.1016/j.ccr.2010.05.026. View

Calleja V, Alcor D, Laguerre M, Park J, Vojnovic B, Hemmings B . Intramolecular and intermolecular interactions of protein kinase B define its activation in vivo. PLoS Biol. 2007; 5(4):e95. PMC: 1845162. DOI: 10.1371/journal.pbio.0050095. View

Baum C, Ockers S, English B, Price D, Sartor O, Figg W . Androgen receptor sequence and variations in several common prostate cancer cell lines. Cancer Biol Ther. 2010; 9(5):383-8. PMC: 2874092. DOI: 10.4161/cbt.9.5.10891. View

Hers I, Vincent E, Tavare J . Akt signalling in health and disease. Cell Signal. 2011; 23(10):1515-27. DOI: 10.1016/j.cellsig.2011.05.004. View

Beatson E, Chau C, Price D, Figg W . PARP inhibitors on the move in prostate cancer: spotlight on Niraparib & update on PARP inhibitor combination trials. Am J Clin Exp Urol. 2022; 10(4):252-257. PMC: 9428566. View

Adzhubei I, Jordan D, Sunyaev S . Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. 2013; Chapter 7:Unit7.20. PMC: 4480630. DOI: 10.1002/0471142905.hg0720s76. View

Maehama T, Dixon J . The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1998; 273(22):13375-8. DOI: 10.1074/jbc.273.22.13375. View

Robinson D, Van Allen E, Wu Y, Schultz N, Lonigro R, Mosquera J . Integrative clinical genomics of advanced prostate cancer. Cell. 2015; 161(5):1215-1228. PMC: 4484602. DOI: 10.1016/j.cell.2015.05.001. View

10.

Kaiser A, Attardi L . Deconstructing networks of p53-mediated tumor suppression in vivo. Cell Death Differ. 2017; 25(1):93-103. PMC: 5729531. DOI: 10.1038/cdd.2017.171. View

11.

Tate J, Bamford S, Jubb H, Sondka Z, Beare D, Bindal N . COSMIC: the Catalogue Of Somatic Mutations In Cancer. Nucleic Acids Res. 2018; 47(D1):D941-D947. PMC: 6323903. DOI: 10.1093/nar/gky1015. View

12.

Kopic S, Eirich K, Schuster B, Hanenberg H, Varon-Mateeva R, Rittinger O . Hepatoblastoma in a 4-year-old girl with Fanconi anaemia. Acta Paediatr. 2010; 100(5):780-3. DOI: 10.1111/j.1651-2227.2010.02116.x. View

13.

Van Bokhoven A, Varella-Garcia M, Korch C, Johannes W, Smith E, Miller H . Molecular characterization of human prostate carcinoma cell lines. Prostate. 2003; 57(3):205-25. DOI: 10.1002/pros.10290. View

14.

Suzuki H, Freije D, Nusskern D, Okami K, Cairns P, Sidransky D . Interfocal heterogeneity of PTEN/MMAC1 gene alterations in multiple metastatic prostate cancer tissues. Cancer Res. 1998; 58(2):204-9. View

15.

Shihab H, Gough J, Cooper D, Stenson P, Barker G, Edwards K . Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models. Hum Mutat. 2012; 34(1):57-65. PMC: 3558800. DOI: 10.1002/humu.22225. View

16.

Wadosky K, Koochekpour S . Molecular mechanisms underlying resistance to androgen deprivation therapy in prostate cancer. Oncotarget. 2016; 7(39):64447-64470. PMC: 5325456. DOI: 10.18632/oncotarget.10901. View

17.

Schmidt K, Huitema A, Chau C, Figg W . Resistance to second-generation androgen receptor antagonists in prostate cancer. Nat Rev Urol. 2021; 18(4):209-226. DOI: 10.1038/s41585-021-00438-4. View

18.

Chakravarty D, Gao J, Phillips S, Kundra R, Zhang H, Wang J . OncoKB: A Precision Oncology Knowledge Base. JCO Precis Oncol. 2017; 2017. PMC: 5586540. DOI: 10.1200/PO.17.00011. View

19.

Vivanco I, Sawyers C . The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2002; 2(7):489-501. DOI: 10.1038/nrc839. View

20.

Fong P, Boss D, Yap T, Tutt A, Wu P, Mergui-Roelvink M . Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009; 361(2):123-34. DOI: 10.1056/NEJMoa0900212. View