Search Results - EGA European Genome-Phenome Archive

Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple negative breast cancer: phase 2 adaptive BELLINI trial. WES

The adaptive BELLINI trial explored whether short combination ICI induces immune activation (primary endpoint: two-fold increase in CD8+ T cells or IFNG), providing rationale for neoadjuvant ICI without chemotherapy. In window of opportunity cohorts A (4 weeks anti-PD1) and B (4 weeks anti-PD1 + anti-CTLA4), we observed immune activation in 53% (8/15) and 60% (9/15) of patients, respectively. High tumor-infiltrating lymphocytes (TILs) correlated with response. Based on these data, we opened cohort C for patients with high TILs (≥50%) who received 6 weeks neoadjuvant anti-PD1 + anti-CTLA4 followed by surgery (primary endpoint: pathological complete response, pCR). 53% (8/15) of patients had major pathological response (< 10% viable tumor) at resection, with 33% (5/15) having pCR. All cohorts met Simon’s two-stage threshold for expansion to stage II. In conclusion, neoadjuvant immunotherapy without chemotherapy demonstrates potential efficacy and warrants further investigation in patients with early TNBC.

Study EGAS50000000568

Molecular subsets in renal cancer determine outcome to checkpoint and angiogenesis blockade

We conducted integrated multi-omics evaluation of 823 tumors from advanced renal cell carcinoma (RCC) patients and identified molecular subsets associated with differential clinical outcomes to angiogenesis blockade alone or with a checkpoint inhibitor. Unsupervised transcriptomic analysis revealed six molecular subsets with distinct angiogenesis, immune, cell cycle, metabolism, and stromal programs. While sunitinib was effective in subsets with high angiogenesis, atezolizumab+bevacizumab improved clinical benefit in tumors with high T-effector and/or cell cycle transcription. Somatic mutations in PBRM1 and KDM5C associated with high angiogenesis and AMPK/Fatty acid oxidation gene expression, while CDKN2A/B and TP53 alterations were more prevalent in tumors with increased cell cycle and anabolic metabolism. Sarcomatoid tumors exhibited low prevalence of PBRM1 mutations and angiogenesis markers, frequent CDKN2A/B, BAP1 and TP53 alterations, and increased PD-L1 expression. These findings can be applied to molecularly stratify advanced RCC patients, explain improved outcomes of sarcomatoid tumors to checkpoint blockade, and develop personalized therapies.

Study EGAS00001004353

BIOKEY: A single-cell catalogue of the dynamic changes underlying Checkpoint Immunotherapy response in Early Breast Cancer

Checkpoint immunotherapy combined with neoadjuvant chemotherapy improves complete pathologic response in a subset of breast cancer patients. Here, we applied single-cell profiling to tumor biopsies collected before and during anti-PD1 therapy. One-third of tumors exhibited proliferative T-cells expanding along CD8+ or CD4+ lineages, which were either characterized by increased cytotoxicity and exhaustion or improved T-helper function, respectively. Lineage tracing in non-expanding tumors revealed at which point in the lineage T-cells were impaired, while gene expression modeling along these lineages revealed novel genes and underlying transcription factors involved in T-cell expansion. Interestingly, different dendritic and myeloid cell phenotypes could either stimulate or inhibit expanding T-cells, while cell-to-cell communication revealed an integrated immune context highly predictive of T-cell expansion, consisting of immune-stimulatory/-inhibitory interactions between cancer and various immune cell types. Our data yield unprecedented insights into the dynamic changes underlying checkpoint immunotherapy response in breast cancer.

Study EGAS00001004809

Transcriptional_analysis_of_cells_from_lungs

To capture the full heterogeneity of the cellular types and states during HSPCs differentiation, haematopoietic progenitors will be obtained through column-enrichment of cells expressing CD34, a pan-progenitor marker for HSPCs. The samples from tumour and non-tumour lung tissue from different patients will be processed using the 10x Genomics platform. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

Study EGAS00001002649

Dataset for Direct Detection of Early-Stage Cancers using Circulating Tumor DNA

The dataset for Direct Detection of Early-Stage Cancers using Circulating Tumor DNA includes 602 bam files from next-generation sequencing on the Illumina HiSeq2500 or MiSeq. The samples analyzed include cancer cell lines as well as plasma and tissue specimens from healthy individuals and patients with cancer.

Dataset EGAD00001003601

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Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple negative breast cancer: phase 2 adaptive BELLINI trial. WES

Molecular subsets in renal cancer determine outcome to checkpoint and angiogenesis blockade

BIOKEY: A single-cell catalogue of the dynamic changes underlying Checkpoint Immunotherapy response in Early Breast Cancer

Transcriptional_analysis_of_cells_from_lungs

Dataset for Direct Detection of Early-Stage Cancers using Circulating Tumor DNA

Genome and transcriptome sequence data from a non-small cell lung cancer patient

Genome and transcriptome sequence data from a metastatic prostate cancer patient

Genome and transcriptome sequence data from a pancreatic adenocarcinoma patient

Genome and transcriptome sequence data from a metastatic paraganglioma patient

Genome and transcriptome sequence data from a metastatic breast cancer patient

Genome and transcriptome sequence data from a solitary fibrous tumors (sarcoma) patient

Genome and transcriptome sequence data from a metastatic rectal cancer patient

Genome and transcriptome sequence data from a chronic lymphocytic leukemia patient

Genome and transcriptome sequence data from a metastatic breast cancer patient

Genome and transcriptome sequence data from a radiation-induced pleomorphic sarcoma patient

Genome and transcriptome sequence data from a metastatic gastric cancer patient

Genome and transcriptome sequence data from a metastatic adenocarcinoma of appendiceal origin patient

Genome and transcriptome sequence data from a salivary duct carcinoma patient

Genome and transcriptome sequence data from a metastatic melanoma patient

Genome and transcriptome sequence data from a metastatic gallbladder cancer patient

Genome and transcriptome sequence data from a metastatic colonic adenocarcinoma patient

Genome and transcriptome sequence data from a metastatic adenocarcinoma of the rectum patient

Genome and transcriptome sequence data from a metastatic breast cancer patient

Genome and transcriptome sequence data from a metastatic small cell carcinoma patient

Genome and transcriptome sequence data from a metastatic serous ovarian cancer patient