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• DAC Recurrent resistance mutations to lirafugratinib delineate treatment sequences for FGFR2-driven tumors

  DAC for Recurrent resistance mutations to lirafugratinib delineate treatment sequences for FGFR2-driven tumors

  Dac EGAC50000000699

• Djerroudi et al., E-cadherin inactivation shapes tumor microenvironment specificities in invasive lobular carcinoma

  Invasive lobular breast carcinoma (ILC) shows specific stromal features, T lymphocyte infiltration (TIL) being associated with poor prognosis. Here, we reveal the involved mechanism by performing single cell RNA sequencing, combined immunohistochemistry, deconvolution of bulk RNA sequencing from large retrospective ILC series, and functional assays using primary cells. We show that ILC accumulate FAP+ inflammatory cancer-associated fibroblasts (iCAF) through a previously undescribed mechanism mediated by E-cadherin/CDH1 on CAF plasticity. Indeed, CDH1 inactivation in ILC cancer cells prevents differentiation of iCAF into myofibroblastic CAF (myCAF), leading to iCAF accumulation. In turn, iCAF increase TIL infiltration and shape their spatial organization in ILC. Subsequently, CDH1-inactivated ILC cancer cells promote immune escape by lack of retention and activation of ITGAE-expressing resident memory CD8+ T lymphocytes (TRM). Hence, our study uncovers reciprocal interactions between CDH1-inactivated cancer cells, iCAF and CD8+ TRM, revealing why and how TILs have a poor prognosis in ILC patients, a mechanism extrapolated to other CDH1-mutated cancer types.

  Study EGAS50000000761

• DOGMA-seq data and analysis

  Data and analysis of DOGMA-seq assay of Lin- sorted live cells from bone marrow tissue of 12 patients with MDS or AML (before treatment with 5-azacytidine). Data files are paired-end reads in FASTQ format from the Illumina NovaSeq 6000 sequencer. Analysis files are outputs from Cellranger ARC: .h5 peaks and genes matrix file, atac_fragments.tsv.gz file and its index. Samples with ADT assay have analysis files from kallisto, bustools, and kite: ADT_features.txt, ADT_barcodes.txt, ADT_matrix.mtx.

  Dataset EGAD50000001377

• Whole exome sequencing of a representative cohort of AML

  The Genomic DNA Clean & Concentrator kit (ZYMO Research) was used to remove EDTA from the DNA samples. Sample libraries were prepared using 100 ng of input according to the KAPA HyperPlus Kit (Roche) using Unique Dual Index adapters (Integrated DNA Technologies, Inc.). Exomes were captured using the SeqCap EZ MedExome (Roche Nimblegen) according to SeqCap EZ HyperCap Library v1.0 Guide (Roche) with the xGen Universal blockers – TS Mix (Integrated DNA Technologies, Inc.). The amplified captured sample libraries were paired-end sequenced (2x100 bp) on the Novaseq 6000 platform (Illumina) and aligned to the hg19 reference genome using the Burrows-Wheeler Aligner (BWA)3, v0.7.15-r1140.

  Dataset EGAD00001007580

• Enzymatic methylation sequencing of rectal mucus from patients suspected to have colorectal cancer

  This dataset contains comprises enzymatic methylation sequencing (EM-Seq) data generated from 208 rectal mucus samples from patients suspected to have colorectal cancer and healthy controls. Targeted CpG sites were enriched using a panel of genes implicated in colorectal cancer, and libraries were prepared with NEBNext EM-Seq prior to Illumina sequencing. Sequencing was performed on the Illumina NovaSeq6000 platform, producing paired-end FASTQ files. These data support analyses of DNA methylation patterns in CRC detection and progression

  Dataset EGAD50000001871

• Healthy control and lung cancer plasma cfDNA samples from various collection tubes

  The dataset contains 6 lung cancer and 60 healthy control plasma cfDNA samples collected in EDTA, PAXGene and Norgen blood collection tubes at various locations. Shallow WGS was performed on an Illumina Novaseq S4 PE150bp. Samples are provided as raw reads without any prior processing.

  Dataset EGAD00001008322

• cfDNA from fractionated and paired unfractionated plasma samples of lung cancer patients

  Plasma from lung cancer patients from EDTA tubes was fractionated using size exclusion chromatography. Fractions 1-5, 7-11, 12-15, 16-20 were pooled, cfDNA was extracted from the fractions and paired unfractionated samples and PE150bp sequencing was performed on an Illumina Novaseq S4 flowcell. Samples are provided as raw reads without any prior processing.

  Dataset EGAD00001009780

• Whole genome sequencing

  This dataset contains whole genome sequencing data from 22 samples of FACS-purified bone marrow CD34+ haematopoietic stem and progenitor cells and matched hair follicle controls collected from individuals undergoing hip replacement surgery. Additionally, it contains whole genome sequencing data from unseparated bone marrow mononuclear cells, CD3-CD34- bone marrow mononuclear cells, and peripheral blood granulocytes of the same 14 samples. Haematopoietic samples were sequenced to a target coverage of 90-120x; 19 of them were re-sequenced to a total target coverage of 270x. Hair follicle controls were sequenced to a target coverage of 30x.

  Dataset EGAD00001015178

• Raw transcriptomic sequencing data from peritoneal metastasis of gastric cancer

  This controlled-access dataset contains raw FASTQ files generated from single-cell RNA sequencing (scRNA-seq) and 10x Genomics Visium spatial transcriptomics. The dataset includes scRNA-seq data from four human lesions of peritoneal metastasis of gastric cancer (PMGC) and Visium spatial transcriptomics data from one human PMGC lesion. It also includes scRNA-seq data from nine PMGC lesions from humanized mouse models engrafted with human gastric cancer cells under different treatment conditions. These data are provided to support transcriptomic analysis of tumor and immune microenvironment features in PMGC.

  Dataset EGAD50000002714

• Total RNA sequencing of 32 chronic lymphocytic leukemia (CLL) patients

  Peripheral blood mononuclear cells (PBMC) of CLL patients were isolated by density-gradient centrifugation over Linfosep (Biomedics, Madrid, Spain). B cells were purified with a CD19+ magnetic-bead system (MidiMACS, Miltenyi Biotec, Bergish Gladbash, Germany) according to the manufacturers’ instructions. Mean B-cell purity was >99% and the mean percentage of CD5+/CD19+ cells after purification was >98%, as measured by flow cytometry. Total RNA was extracted from purified cells in a single step using TriPure Isolation Reagent (Roche Applied Science, Vilvoorde, Belgium).Whole transcriptome sequencing libraries were prepared using the TruSeq Stranded Total RNA Sample Preparation Kit (Illumina). Libraries underwent 2 × 76 bp paired-end sequencing on a HiSeq 2500 instrument (Illumina). The median number of paired-end reads was 60.5 million (range, 49.7-79.7 million).

  Dataset EGAD00001004047