MYC is Sufficient to Generate Mid-Life High-Grade Serous Ovarian and Uterine Serous Carcinomas in a P53-R270H Mouse Model

Overview

Journal Cancer Res Commun

Specialty Oncology

Date 2024 Sep 3

PMID 39225558

Authors

Alexandra Blackman

Amy C Rees

Robert R Bowers

Christian M Jones

Silvia G Vaena

Madison A Clark

Shelby Carter

Evan D Villamor

Della Evans

Anthony J Emanuel

George Fullbright

Matthew S OMalley

Richard L Carpenter

David T Long

Laura S Spruill

Martin J Romeo

Brian C Orr

Kristi L Helke

Joe R Delaney

Affiliations

Soon will be listed here.

Abstract

Significance: Mouse models using transgenes which generate spontaneous cancers are essential tools to examine the etiology of human diseases. Here, the first Myc-driven spontaneous model is described as a valid HGSOC model. Surprisingly, aspects of uterine serous carcinoma were also observed in this model.

Citing Articles

Aggressive Serous Carcinomas of the Female Reproductive Tract: Cancer-Prone Cell States and Genetic Drivers.

Phuong D, Pirtz M, Ralston C, Cosgrove B, Schimenti J, Flesken-Nikitin A Cancers (Basel). 2025; 17(4).

PMID: 40002199 PMC: 11852459. DOI: 10.3390/cancers17040604.

MYC and HSF1 Cooperate to Drive Sensitivity to Polo-like Kinase 1 Inhibitor Volasertib in High-grade Serous Ovarian Cancer.

Williams I, OMalley M, DeHart H, Walker B, Ulhaskumar V, Jothirajah P Cancer Res Commun. 2025; 5(2):253-266.

PMID: 39831777 PMC: 11799878. DOI: 10.1158/2767-9764.CRC-24-0400.

References

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

Leeper K, Garcia R, Swisher E, Goff B, Greer B, Paley P . Pathologic findings in prophylactic oophorectomy specimens in high-risk women. Gynecol Oncol. 2002; 87(1):52-6. DOI: 10.1006/gyno.2002.6779. View

Osoegawa K, Tateno M, Woon P, Frengen E, Mammoser A, Catanese J . Bacterial artificial chromosome libraries for mouse sequencing and functional analysis. Genome Res. 2000; 10(1):116-28. PMC: 310499. View

Motenko H, Neuhauser S, OKeefe M, Richardson J . MouseMine: a new data warehouse for MGI. Mamm Genome. 2015; 26(7-8):325-30. PMC: 4534495. DOI: 10.1007/s00335-015-9573-z. View

Domcke S, Sinha R, Levine D, Sander C, Schultz N . Evaluating cell lines as tumour models by comparison of genomic profiles. Nat Commun. 2013; 4:2126. PMC: 3715866. DOI: 10.1038/ncomms3126. View

Zhang S, Dolgalev I, Zhang T, Ran H, Levine D, Neel B . Both fallopian tube and ovarian surface epithelium are cells-of-origin for high-grade serous ovarian carcinoma. Nat Commun. 2019; 10(1):5367. PMC: 6879755. DOI: 10.1038/s41467-019-13116-2. View

Dobin A, Davis C, Schlesinger F, Drenkow J, Zaleski C, Jha S . STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2012; 29(1):15-21. PMC: 3530905. DOI: 10.1093/bioinformatics/bts635. View

Akbay E, Pena C, Ruder D, Michel J, Nakada Y, Pathak S . Cooperation between p53 and the telomere-protecting shelterin component Pot1a in endometrial carcinogenesis. Oncogene. 2012; 32(17):2211-9. PMC: 3636499. DOI: 10.1038/onc.2012.232. View

Jacks T, Remington L, Williams B, Schmitt E, Halachmi S, Bronson R . Tumor spectrum analysis in p53-mutant mice. Curr Biol. 1994; 4(1):1-7. DOI: 10.1016/s0960-9822(00)00002-6. View

10.

Ghandi M, Huang F, Jane-Valbuena J, Kryukov G, Lo C, McDonald 3rd E . Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature. 2019; 569(7757):503-508. PMC: 6697103. DOI: 10.1038/s41586-019-1186-3. View

11.

Hamilton C, Cheung M, Osann K, Chen L, Teng N, Longacre T . Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer. 2006; 94(5):642-6. PMC: 2361201. DOI: 10.1038/sj.bjc.6603012. View

12.

Chowdhury S, Kennedy J, Ivey R, Murillo O, Hosseini N, Song X . Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer. Cell. 2023; 186(16):3476-3498.e35. PMC: 10414761. DOI: 10.1016/j.cell.2023.07.004. View

13.

Isaka K, Nishi H, Sagawa Y, Nakada T, Osakabe Y, Serizawa H . Establishment of a new human cell line (EN) with TP53 mutation derived from endometrial carcinoma. Cancer Genet Cytogenet. 2003; 141(1):20-5. DOI: 10.1016/s0165-4608(02)00673-8. View

14.

Xiao G, Lundine D, Annor G, Canar J, Ellison V, Polotskaia A . Gain-of-Function Mutant p53 R273H Interacts with Replicating DNA and PARP1 in Breast Cancer. Cancer Res. 2019; 80(3):394-405. PMC: 7002183. DOI: 10.1158/0008-5472.CAN-19-1036. View

15.

Lu K, Broaddus R . Endometrial Cancer. N Engl J Med. 2020; 383(21):2053-2064. DOI: 10.1056/NEJMra1514010. View

16.

Liao Y, Smyth G, Shi W . featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2013; 30(7):923-30. DOI: 10.1093/bioinformatics/btt656. View

17.

Sherman B, Hao M, Qiu J, Jiao X, Baseler M, Lane H . DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022; 50(W1):W216-W221. PMC: 9252805. DOI: 10.1093/nar/gkac194. View

18.

Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin A, Kim S . The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012; 483(7391):603-7. PMC: 3320027. DOI: 10.1038/nature11003. View

19.

Clark-Knowles K, Senterman M, Collins O, Vanderhyden B . Conditional inactivation of Brca1, p53 and Rb in mouse ovaries results in the development of leiomyosarcomas. PLoS One. 2010; 4(12):e8534. PMC: 2795167. DOI: 10.1371/journal.pone.0008534. View

20.

Connolly D, Bao R, Nikitin A, Stephens K, Poole T, Hua X . Female mice chimeric for expression of the simian virus 40 TAg under control of the MISIIR promoter develop epithelial ovarian cancer. Cancer Res. 2003; 63(6):1389-97. View