Dataset Information

Integrated cellular and plasma proteomics reveals common and systemic signatures in contrasting B-cell cancers

ABSTRACT: Approximately 800,000 leukaemia and lymphoma cases are diagnosed worldwide each year. Burkitt’s lymphoma and chronic lymphocytic leukaemia represent contrasting examples of B-cell cancers, modelled by Eμ-myc and Eμ-TCL1 mice, respectively. To better understand B-cell cancers and systemic effects of oncogenesis, tumours and plasma from these models were profiled by mass spectrometry proteomics. 8270 cellular and 2095 plasma proteins were fully quantitated by isobaric labelling, of which 695 and 279 demonstrated overabundance coinciding in both tumour models, respectively. Co-occurring upregulated cellular tumour processes included ribosome biogenesis, translation, cell cycle promotion and chromosome segregation. Tumour plasma overabundance highlighted immunity, inflammation, microenvironment interactions, a prolific tumour lysis signature and putative biomarkers of early-stage cancer. Integrative evaluation of tumours and plasma provided systemic insight not captured in isolation. Overall, these findings provide a detailed characterisation of systemic oncogenesis in two contrasting B-cell tumour models, identifying extensive common profiles in both tumour cells and plasma.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Spleen, B Cell, Primary Cell, Blood Plasma, B-lymphocyte, B-cell Lymphoma Cell, B-cell Leukemia Cell

DISEASE(S): Chronic Lymphocytic Leukemia,Leukemia,Burkitt Lymphoma,Lymphoma

SUBMITTER: Harvey Johnston

LAB HEAD: Spiro Dennis Garbis

PROVIDER: PXD004608 | Pride | 2017-01-10

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	020913_BCellsMycTCL1_20.raw	Raw
	020913_BCellsMycTCL1_20_5.raw	Raw
	020913_BCellsMycTCL1_21.raw	Raw
	020913_BCellsMycTCL1_22.raw	Raw
	020913_BCellsMycTCL1_23.raw	Raw

Items per page:

1 - 5 of 172

Publications

Integrated Cellular and Plasma Proteomics of Contrasting B-cell Cancers Reveals Common, Unique and Systemic Signatures.

Johnston Harvey E HE Carter Matthew J MJ Cox Kerry L KL Dunscombe Melanie M Manousopoulou Antigoni A Townsend Paul A PA Garbis Spiros D SD Cragg Mark S MS

Molecular & cellular proteomics : MCP 20170104 3

Approximately 800,000 leukemia and lymphoma cases are diagnosed worldwide each year. Burkitt's lymphoma (BL) and chronic lymphocytic leukemia (CLL) are examples of contrasting B-cell cancers; BL is a highly aggressive lymphoid tumor, frequently affecting children, whereas CLL typically presents as an indolent, slow-progressing leukemia affecting the elderly. The B-cell-specific overexpression of the <i>myc</i> and <i>TCL1</i> oncogenes in mice induce spontaneous malignancies modeling BL and CLL, ...[more]

PMID: 28062796

Similar Datasets

Project description:Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer with high intra-tumoral heterogeneity, frequently resistant to treatment and no known targeted therapy available to improve patient outcomes. It has been hypothesized that the genomic architecture of a TNBC tumour evolves over time, both before, and during therapy, leading to therapy resistance and a high propensity to relapse. Whether this is an inherent property of the tumour or acquired over time is not well characterized. Despite this important clinical implication, limited studies have been carried out to unravel temporal evolution of TNBC over time. Herein, we report an OMICS based analysis of three TNBC patients who were longitudinally sampled during their treatment at different times of relapse. We recruited three TNBC patients at the time of their first relapse who were then followed-up through the course of their treatment. We obtained retrospective samples (tumour samples) from patient tumours at diagnosis (before neo-adjuvant chemotherapy - NACT) at surgery (post NACT) and prospectively sampled them at each subsequent relapse (tumour, blood plasma, and buffy coat) as determined by RECIST criteria. Tumor and buffy coat DNA were subjected to whole exome sequencing (WES) at 200x, and SNP arrays for copy number variation (CNV) analysis. RNA from tumour samples at relapse was subjected to whole transcriptome sequencing. Pathogenic germline BRCA1 variants identified in WES were validated using Sanger sequencing. 1084 somatic mutations identified in whole exome sequencing of all tumour tissues (n=13) from three patients, were subjected to a custom amplicon ultra-deep sequencing assay at 30,000X in their germline DNA (n=3), tumour DNA (n=10), and cfDNA from plasma samples at relapse (n=8). Copy number corrected allele frequencies, tumour ploidy, tumour purity, and ultra-deep sequencing assay derived variant allele frequencies were used to infer clonal and phylogenetic architecture of each patient as it evolved under selective pressure of therapy over time. Clonality analysis incorporating allele fractions from ultra-deep sequencing identified clones comprising of mutations that are present throughout the course of therapy which we term as founding clones and stem mutations respectively. Such founding clones comprising of stem mutations in all 3 patients were present throughout the course of treatment, irrespective of change in treatment modalities. These stem clones included well characterized cancer related genes like PDGFRB & ARID2 (Patient 02), TP53, BRAF & CSF3R (Patient 04) and ESR1, APC, EZH2 & TP53 (Patient 07). Such branching evolution is seen in all three patients wherein the dominant clone (stem clone) acquires additional mutations to form sub-clones, while persisting over time. These sub-clones may be chemo and radio resistant, while also providing for organ specific metastatic potential. Allele fractions of expressed variants inferred from RNA-Seq data co-related with allele fractions from WES data indicating that all somatic.