A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer

Kaur, Pushpinder; Campo, Daniel; Porras, Tania B.; Ring, Alexander; Lu, Janice; Chairez, Yvonne; Su, Yeping; Kang, Irene; Lang, Julie E.

doi:10.3390/ijms21144826

Cited by 9 publications

(6 citation statements)

References 83 publications

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“…To get one step forward, and acknowledging both, the growing trend of last decades towards de-escalating surgical procedures not only on primary breast cancer but also on axillary nodes 10,12 , and the technical difficulties of sampling and processing different metastatic sites 13 , we hypothesized that liquid could replace tissue biopsies. Indeed, although rather preliminary, our data support the role of CTCs as a tissue-surrogate.…”

Section: Discussionmentioning

confidence: 99%

Copy number alterations analysis of primary tumor tissue and circulating tumor cells from patients with early-stage triple negative breast cancer

Silvestri

Dugo

Vismara

et al. 2022

Sci Rep

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Triple negative breast cancer (TNBC) is characterized by clinical aggressiveness, lack of recognized target therapy, and a dismal patient prognosis. Several studies addressed genomic changes occurring during neoadjuvant chemotherapy (NAC) focusing on somatic variants, but without including copy number alterations (CNAs). We analyzed CNA profiles of 31 TNBC primary tumor samples before and after NAC and of 35 single circulating tumor cells (CTCs) collected prior, during and after treatment by using next-generation sequencing targeted profile and low-pass whole genome sequencing, respectively. In pre-treatment tissue samples, the most common gains occurred on chromosomes 1, 2 and 8, and SOX11 and MYC resulted the most altered genes. Notably, amplification of MSH2 (4/4 versus 0/12, p < 0.01) and PRDM1 and deletion of PAX3 (4/4 versus 1/12, p < 0.01) significantly characterized primary tumors of patients with pathological complete response. All patients with paired pre- and post-NAC samples reported a change in post-treatment CNAs compared to baseline, despite they showed at least one common alteration. CNAs detected after treatment involved genes within druggable pathways such as EGFR, cell cycle process and Ras signaling. In two patients, CTCs shared more alterations with residual rather than primary tumor involving genes such as MYC, BCL6, SOX2, FGFR4. The phylogenetic analysis of CTCs within a single patient revealed NAC impact on tumor evolution, suggesting a selection of driver events under treatment pressure. In conclusion, our data showed how chemoresistance might arise early from treatment-induced selection of clones already present in the primary tumor, and that the characterization of CNAs on single CTCs informs on cancer evolution and potential druggable targets.

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Section: Discussionmentioning

confidence: 99%

Copy number alterations analysis of primary tumor tissue and circulating tumor cells from patients with early-stage triple negative breast cancer

Silvestri

Dugo

Vismara

et al. 2022

Sci Rep

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“…The RNA-seq method described above was validated in whole-transcriptome profiling studies in CTC from patients with non-metastatic breast cancer (stage II-III). These studies’ procedures and results were previously reported [ 28 , 29 ], and the results demonstrated that CTCs from patients with MBC could be used to generate cDNA libraries of sufficient quantity and quality that enable whole-genome sequencing.…”

Section: Methodsmentioning

confidence: 54%

A Multi-Center Clinical Study to Harvest and Characterize Circulating Tumor Cells from Patients with Metastatic Breast Cancer Using the Parsortix® PC1 System

Cohen

Jayachandran

Moore

et al. 2022

Cancers

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Circulating tumor cells (CTCs) captured from the blood of cancer patients may serve as a surrogate source of tumor material that can be obtained via a venipuncture (also known as a liquid biopsy) and used to better understand tumor characteristics. However, the only FDA-cleared CTC assay has been limited to the enumeration of surface marker–defined cells and not further characterization of the CTCs. In this study, we tested the ability of a semi-automated device capable of capturing and harvesting CTCs from peripheral blood based on cell size and deformability, agnostic of cell-surface markers (the Parsortix® PC1 System), to yield CTCs for evaluation by downstream techniques commonly available in clinical laboratories. The data generated from this study were used to support a De Novo request (DEN200062) for the classification of this device, which the FDA recently granted. As part of a multicenter clinical trial, peripheral blood samples from 216 patients with metastatic breast cancer (MBC) and 205 healthy volunteers were subjected to CTC enrichment. A board-certified pathologist enumerated the CTCs from each participant by cytologic evaluation of Wright-Giemsa-stained slides. As proof of principle, cells harvested from a concurrent parallel sample provided by each participant were evaluated using one of three additional evaluation techniques: molecular profiling by qRT-PCR, RNA sequencing, or cytogenetic analysis of HER2 amplification by FISH. The study demonstrated that the Parsortix® PC1 System can effectively capture and harvest CTCs from the peripheral blood of MBC patients and that the harvested cells can be evaluated using orthogonal methodologies such as gene expression and/or Fluorescence In Situ Hybridization (FISH).

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“…The formidable heterogeneity of breast cancer forbids us from covering all patients with a single treatment strategy ( 18 ). Additionally, over the lengthy course of treatment, tumor cells frequently undergo mutation, resulting in resistance to the existing treatment regimens ( 19 ). This condition spurs us to delve more deeply into breast tumor cells’ physiological processes and discover the mechanisms underlying their development and death.…”

Section: Discussionmentioning

confidence: 99%

A signature of cuproptosis-related lncRNAs predicts prognosis and provides basis for future anti-tumor drug development in breast cancer

Yu¹,

Liu²,

Zhang³

et al. 2023

Transl Cancer Res

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Background Breast cancer is the most prevalent malignancy worldwide and the leading culprit for women’s death. Cuproptosis is a novel and promising modality of tumor cell death and the relationship with long non-coding RNAs (lncRNAs) remains shrouded in a veil. Studies in cuproptosis-related lncRNAs can aid in the clinical management of breast cancer and provide a basis for anti-tumor drug development. Methods RNA-Seq data, somatic mutation data, and clinical information were downloaded from The Cancer Genome Atlas (TCGA). Patients were divided into high- and low-risk groups according to the risk score. Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were used to select prognostic lncRNAs to construct a risk score system. Its’ prognostic value was confirmed in the training and validation cohorts subsequently. Functional analysis regarding cuproptosis-related lncRNAs was performed. Results Eighteen cuproptosis-related lncRNAs were identified and 11 of them including AL023882.1 , AC091588.1 , AC138028.2 , AC027514.1 , AL592301.1 , LRRC8C-DT , MFF-DT , NIFK-AS1 , MECOM-AS1 , OTUD6B-AS1 and RNF32-AS1 were selected for risk score system construction. The risk score was confirmed as an independent prognostic factor and patients in the high-risk group had a worse prognosis. A nomogram based on the independent prognostic factors was constructed for clinical decision aids. Further analyses revealed that patients in the high-risk group faced a heavier tumor mutational burden (TMB) and suppressed anti-tumor immunity. Besides, cuproptosis-related lncRNAs were associated with the expression of immune checkpoint inhibitors, N6-adenylate methylation (m6a), and drug sensitivity in breast cancer. Conclusions A prognostic risk score system with satisfactory predictive accuracy was constructed. Besides, cuproptosis-related lncRNAs can influence the immune microenvironment, TMB, m6a, and drug sensitivity in breast cancer, which may provide a basis for future anti-tumor drug development.

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A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer

Cited by 9 publications

References 83 publications

Copy number alterations analysis of primary tumor tissue and circulating tumor cells from patients with early-stage triple negative breast cancer

Copy number alterations analysis of primary tumor tissue and circulating tumor cells from patients with early-stage triple negative breast cancer

A Multi-Center Clinical Study to Harvest and Characterize Circulating Tumor Cells from Patients with Metastatic Breast Cancer Using the Parsortix® PC1 System

A signature of cuproptosis-related lncRNAs predicts prognosis and provides basis for future anti-tumor drug development in breast cancer

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