Genomic and expression profiling reveal molecular heterogeneity of disseminated tumor cells in bone marrow of early breast cancer

NPJ Breast Cancer
Mark Jesus M MagbanuaJohn W Park

Abstract

Detection of disseminated tumor cells (DTCs) in bone marrow is an established negative prognostic factor. We isolated small pools of (~20) EPCAM-positive DTCs from early breast cancer patients for genomic profiling. Genome-wide copy number profiles of DTC pools (n = 45) appeared less aberrant than the corresponding primary tumors (PT, n = 16). PIK3CA mutations were detected in 26% of DTC pools (n = 53), none of them were shared with matched PTs. Expression profiling of DTC pools (n = 30) confirmed the upregulation of EPCAM expression and certain oncogenes (e.g., MYC and CCNE1), as well as the absence of hematopoietic features. Two expression subtypes were observed: (1) luminal with dual epithelial-mesenchymal properties (high ESR1 and VIM/CAV1 expression), and (2) basal-like with proliferative/stem cell-like phenotype (low ESR1 and high MKI67/ALDH1A1 expression). We observed high discordance between ESR1 (40%) and ERRB2 (43%) expression in DTC pools vs. the clinical ER and HER2 status of the corresponding primary tumors, suggesting plasticity of biomarker status during dissemination to the bone marrow. Comparison of expression profiles of DTC pools with available data from circulating tumor cells (CTCs) of metastatic breast can...Continue Reading

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Citations

Aug 24, 2019·Frontiers in Endocrinology·María Inés Diaz BessoneMarina Simian
May 31, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mark Jesus M MagbanuaJohn W Park
Apr 21, 2021·Nature Reviews. Clinical Oncology·Lorenz C HofbauerKlaus Pantel
May 21, 2021·Clinical & Experimental Metastasis·Saraswoti KhadgeJames E Talmadge
May 21, 2021·Frontiers in Immunology·Amrita BasuKrithika Kodumudi
Jun 25, 2021·Science Advances·Zeru TianHan Xiao

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Methods Mentioned

BETA
fluorescence-activated cell sorting
FACS
Bone marrow aspiration
flow
PCR

Software Mentioned

Variant Effect Scoring Tool
Limma
geNorm
Bioconductor
Related Analysis of Variants Toolkit
R package genefu
R package Rtnse
RealTime StatMiner
R
Cancer

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