Digital droplet PCR analysis of organoids generated from mouse mammary tumors demonstrates proof-of-concept capture of tumor heterogeneity

Katherine E Lake; Megan M Colonnetta; Clayton A Smith; Kaitlyn Saunders; Kenneth Martinez-Algarin; Sakshi Mohta; Jacob Pena; Heather L McArthur; Sangeetha M Reddy; Evanthia T Roussos Torres; Elizabeth H Chen; Isaac S Chan

doi:10.3389/fcell.2024.1358583

Digital droplet PCR analysis of organoids generated from mouse mammary tumors demonstrates proof-of-concept capture of tumor heterogeneity

Front Cell Dev Biol. 2024 May 15:12:1358583. doi: 10.3389/fcell.2024.1358583. eCollection 2024.

Authors

Katherine E Lake^{1

2}, Megan M Colonnetta^{2

3

4

5}, Clayton A Smith^{1

2}, Kaitlyn Saunders^{1

2}, Kenneth Martinez-Algarin^{1

2}, Sakshi Mohta^{1

2}, Jacob Pena^{1

2}, Heather L McArthur^{1

2}, Sangeetha M Reddy^{1

2}, Evanthia T Roussos Torres⁶, Elizabeth H Chen^{2

3

4

5}, Isaac S Chan^{1

2

3

4}

Affiliations

¹ Department of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern, Dallas, TX, United States.
² Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States.
³ Department of Molecular Biology, University of Texas Southwestern, Dallas, TX, United States.
⁴ Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.
⁵ Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, United States.
⁶ Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.

Abstract

Breast cancer metastases exhibit many different genetic alterations, including copy number amplifications (CNA). CNA are genetic alterations that are increasingly becoming relevant to breast oncology clinical practice. Here we identify CNA in metastatic breast tumor samples using publicly available datasets and characterize their expression and function using a metastatic mouse model of breast cancer. Our findings demonstrate that our organoid generation can be implemented to study clinically relevant features that reflect the genetic heterogeneity of individual tumors.

Keywords: FGFR1; breast cancer; ddPCR; heterogeneity; metastasis.

Grants and funding

K08 CA270188/CA/NCI NIH HHS/United States