Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The spatio-temporal evolution of lymph node spread in early breast cancer

ABSTRACT: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localised and systemic disease is key to understanding breast cancer progression, however our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data derives from primary tumours. In 11 treatment-naïve node positive early breast cancer patients without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multi-region sequencing of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumour DNA (ctDNA). Linear evolution from primary to lymph node was rare (1/11) whereas the majority of cases displayed either early divergence between primary and nodes (4/11), or no detectable divergence (6/11) where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic clones was driven in part by APOBEC. Longitudinal ctDNA from 2 subjects taken peri-operatively reflected the two major evolutionary patterns and demonstrates, even in this early disease cohort, the principle of detection of private mutations from an early metastatic nodal deposit. This study sheds new light on a crucial evolutionary step in the natural history of breast cancer.

SUBMITTER: Peter Barry

PROVIDER: S-BSST110 | bioimages |

REPOSITORIES: bioimages

ACCESS DATA

Json Xml

Similar Datasets

The spatio-temporal evolution of lymph node spread in early breast cancer

Project description:Purpose: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localised and systemic disease is key to understanding breast cancer progression, however our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data derive from primary tumours. Experimental design: In 11 treatment-naïve node positive early breast cancer patients without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multi-region sequencing (n=78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumour DNA (ctDNA). Results: Linear evolution from primary to lymph node was rare (1/11) whereas the majority of cases displayed either early divergence between primary and nodes (4/11), or no detectable divergence (6/11) where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 subjects taken peri-operatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA.Conclusions: This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients.

| EGAS00001002947 | EGA

The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer.

Project description:Purpose: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localized and systemic disease is key to understanding breast cancer progression; however, our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data are derived from primary tumors.Experimental Design: In 11 patients with treatment-naïve node-positive early breast cancer without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multiregion sequencing (n = 78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumor DNA (ctDNA).Results: Linear evolution from primary to lymph node was rare (1/11), whereas the majority of cases displayed either early divergence between primary and nodes (4/11) or no detectable divergence (6/11), where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 of 7 subjects with evaluable plasma taken perioperatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA.Conclusions: This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients. Clin Cancer Res; 24(19); 4763-70. ©2018 AACR.

| S-EPMC6296441 | biostudies-literature

Omics Integration Analyses Reveal the Early Evolution of Malignancy in Breast Cancer.

Project description:The majority of cancer evolution studies involve individual-based approaches that neglect the population dynamics necessary to build a global picture of cancer evolution for each cancer type. Here, we conducted a population-based study in breast cancer to understand the timing of malignancy evolution and its correlation to the genetic evolution of pathological stages. In an omics integrative approach, we integrated gene expression and genomic aberration data for pre-invasive (ductal carcinoma in situ; DCIS, early-stage) and post-invasive (invasive ductal carcinoma; IDC, late-stage) samples and investigated the evolutionary role of further genetic changes in later stages compared to the early ones. We found that single gene alterations (SGAs) and copy-number alterations (CNAs) work together in forward and backward evolution manners to fine-tune the signaling pathways operating in tumors. Analyses of the integrated point mutation and gene expression data showed that (i) our proposed fine-tuning concept is also applicable to metastasis, and (ii) metastases sometimes diverge from the primary tumor at the DCIS stage. Our results indicated that the malignant potency of breast tumors is constant over the pre- and post-invasive pathological stages. Indeed, further genetic alterations in later stages do not establish de novo malignancy routes; however, they serve to fine-tune antecedent signaling pathways.

| S-EPMC7352609 | biostudies-literature

Early Diagnosis of Breast Cancer.

Project description:Early-stage cancer detection could reduce breast cancer death rates significantly in the long-term. The most critical point for best prognosis is to identify early-stage cancer cells. Investigators have studied many breast diagnostic approaches, including mammography, magnetic resonance imaging, ultrasound, computerized tomography, positron emission tomography and biopsy. However, these techniques have some limitations such as being expensive, time consuming and not suitable for young women. Developing a high-sensitive and rapid early-stage breast cancer diagnostic method is urgent. In recent years, investigators have paid their attention in the development of biosensors to detect breast cancer using different biomarkers. Apart from biosensors and biomarkers, microwave imaging techniques have also been intensely studied as a promising diagnostic tool for rapid and cost-effective early-stage breast cancer detection. This paper aims to provide an overview on recent important achievements in breast screening methods (particularly on microwave imaging) and breast biomarkers along with biosensors for rapidly diagnosing breast cancer.

| S-EPMC5539491 | biostudies-other

Partial breast irradiation for early breast cancer.

Project description: Not available

| S-EPMC6457864 | biostudies-literature

Breast Cancer Family Registry Early-onset Breast Cancer GWAS

Project description:Breast Cancer Family Registry Early-onset Breast Cancer GWAS

| PRJNA454751 | ENA

Breast Cancer Family Registry Early-onset Breast Cancer GWAS

Project description:Breast Cancer Family Registry Early-onset Breast Cancer GWAS

| PRJNA454752 | ENA

Partial breast irradiation techniques in early breast cancer.

Project description:Whole breast irradiation represents an integral part of combined breast-conserving treatment of early breast cancer. A new concept includes replacing traditionally fractionated whole breast postoperative radiotherapy by accelerated partial breast irradiation. The latter involves a variety of techniques and may be applied intraoperatively or shortly after the surgery. The intraoperative techniques include photon or electron external beam irradiation and interstitial high dose rate (HDR) brachytherapy, whereas the postoperative techniques comprise interstitial brachytherapy, be it HDR, pulse dose rate (PDR) or low dose rate (LDR), intracavitary brachytherapy and external beam radiotherapy using electrons, photons or protons. This article presents accelerated partial breast irradiation techniques, ongoing phase III trials evaluating their value and recommendations for clinical practice.

| S-EPMC3863308 | biostudies-other

Temporal and structural evolution of the Early Palæogene rocks of the Seychelles microcontinent.

Project description:The Early Palæogene Silhouette/North Island volcano-plutonic complex was emplaced during the rifting of the Seychelles microcontinent from western India. The complex is thought to have been emplaced during magnetochron C28n. However, the magnetic polarities of the rocks are almost entirely reversed and inconsistent with a normal polarity. In this study we present new in situ zircon U/Pb geochronology of the different intrusive facies of the Silhouette/North Island complex in order to address the timing of emplacement and the apparent magnetic polarity dichotomy. The rocks from Silhouette yielded weighted mean 206Pb/238U ages from 62.4 ± 0.9 Ma to 63.1 ± 0.9 Ma whereas the rocks from North Island yielded slightly younger mean ages between 60.6 ± 0.7 Ma to 61.0 ± 0.8 Ma. The secular latitudinal variation from Silhouette to North Island is consistent with the anticlockwise rotation of the Seychelles microcontinent and the measured polarities. The rocks from Silhouette were emplaced across a polarity cycle (C26r-C27n-C27r) and the rocks from North Island were emplaced entirely within a magnetic reversal (C26r). Moreover, the rocks from North Island and those from the conjugate margin of India are contemporaneous and together mark the culmination of rift-related magmatism.

| S-EPMC5428008 | biostudies-literature

Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution.

Project description:APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast ductal carcinoma in situ, and in preinvasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx preinvasive to invasive non-small cell lung cancer (NSCLC) lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in preinvasive disease, providing fuel for selection early in cancer evolution. SIGNIFICANCE: This study reveals the dynamics and drivers of APOBEC3 gene expression in preinvasive disease and the exacerbation of cellular diversity by APOBEC3B through DNA replication stress to promote chromosomal instability early in cancer evolution.This article is highlighted in the In This Issue feature, p. 2355.

| S-EPMC8487921 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data