Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Identification of ERBB pathway-activated cells in triple-negative breast cancer

  • Cho, Soo Young (Clinical Genomics Analysis Branch, National Cancer Center)
  • Received : 2018.12.10
  • Accepted : 2018.12.31
  • Published : 2019.03.31
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Abstract

Intratumor heterogeneity within a single tumor mass is one of the hallmarks of malignancy and has been reported in various tumor types. The molecular characterization of intratumor heterogeneity in breast cancer is a significant challenge for effective treatment. Using single-cell RNA sequencing (RNA-seq) data from a public resource, an ERBB pathway activated triple-negative cell population was identified. The differential expression of three subtyping marker genes (ERBB2, ESR1, and PGR) was not changed in the bulk RNA-seq data, but the single-cell transcriptomes showed intratumor heterogeneity. This result shows that ERBB signaling is activated using an indirect route and that the molecular subtype is changed on a single-cell level. Our data propose a different view on breast cancer subtypes, clarifying much confusion in this field and contributing to precision medicine.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90. https://doi.org/10.3322/caac.20107
  2. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001;98:10869-10874. https://doi.org/10.1073/pnas.191367098
  3. Jezequel P, Loussouarn D, Guerin-Charbonnel C, Campion L, Vanier A, Gouraud W, et al. Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response. Breast Cancer Res 2015;17:43. https://doi.org/10.1186/s13058-015-0550-y
  4. Chung W, Eum HH, Lee HO, Lee KM, Lee HB, Kim KT, et al. Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer. Nat Commun 2017;8:15081. https://doi.org/10.1038/ncomms15081
  5. Bastien RR, Rodriguez-Lescure A, Ebbert MT, Prat A, Munarriz B, Rowe L, et al. PAM50 breast cancer subtyping by RT-qPCR and concordance with standard clinical molecular markers. BMC Med Genomics 2012;5:44. https://doi.org/10.1186/1755-8794-5-44
  6. Hatakeyama M, Yumoto N, Yu X, Shirouzu M, Yokoyama S, Konagaya A. Transformation potency of ErbB heterodimer signaling is determined by B-Raf kinase. Oncogene 2004;23:5023-5031. https://doi.org/10.1038/sj.onc.1207664
  7. Dan S, Okamura M, Seki M, Yamazaki K, Sugita H, Okui M, et al. Correlating phosphatidylinositol 3-kinase inhibitor efficacy with signaling pathway status: in silico and biological evaluations. Cancer Res 2010;70:4982-4994. https://doi.org/10.1158/0008-5472.CAN-09-4172