Transcriptomic Profiling Reveals Novel Candidate Genes and Signalling Programs in Breast Cancer Quiescence and Dormancy.

QUAYLE, Lewis A., SPICER, Amy, OTTEWELL, Penelope D and HOLEN, Ingunn (2021). Transcriptomic Profiling Reveals Novel Candidate Genes and Signalling Programs in Breast Cancer Quiescence and Dormancy. Cancers, 13 (16): 13163922.

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Abstract

Metastatic recurrence, the major cause of breast cancer mortality, is driven by reactivation of dormant disseminated tumour cells that are defined by mitotic quiescence and chemoresistance. The molecular mechanisms underpinning mitotic quiescence in cancer are poorly understood, severely limiting the development of novel therapies for removal of residual, metastasis-initiating tumour cells. Here, we present a molecular portrait of the quiescent breast cancer cell transcriptome across the four main breast cancer sub-types (luminal, HER2-enriched, basal-like and claudin-low) and identify a novel quiescence-associated 22-gene signature using an established lipophilic-dye (Vybrant® DiD) retention model and whole-transcriptomic profiling (mRNA-Seq). Using functional association network analysis, we elucidate the molecular interactors of these signature genes. We then go on to demonstrate that our novel 22-gene signature strongly correlates with low tumoural proliferative activity, and with dormant disease and late metastatic recurrence (≥5 years after primary tumour diagnosis) in metastatic breast cancer in multiple clinical cohorts. These genes may govern the formation and persistence of disseminated tumour cell populations responsible for breast cancer recurrence, and therefore represent prospective novel candidates to inform future development of therapeutic strategies to target disseminated tumour cells in breast cancer, eliminate minimal residual disease and prevent metastatic recurrence.

Item Type:	Article
Uncontrolled Keywords:	RNA-Seq; breast cancer; dormancy; quiescence; transcriptomics; 1112 Oncology and Carcinogenesis; 3211 Oncology and carcinogenesis
Identification Number:	https://doi.org/10.3390/cancers13163922
SWORD Depositor:	Symplectic Elements
Depositing User:	Symplectic Elements
Date Deposited:	04 Jan 2024 14:44
Last Modified:	04 Jan 2024 14:45
URI:	https://shura.shu.ac.uk/id/eprint/32897

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