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• Discovering novel mechanisms of taxane resistance in human breast cancer by whole-exome sequencing

  Taxanes are key drugs in the treatment of breast cancer, but some breast cancers are resistant to taxanes. Obtaining extensive genomic information in a short time has recently become possible. We used whole exome-sequencing (WES) to investigate mechanisms of taxane resistance in human breast cancer. We selected six patients with breast cancer whose tumors responded well to anthracycline treatment but grew rapidly during neoadjuvant taxane-based chemotherapy. We then performed WES of these samples and identified somatic mutations of candidate genes that are thought to affect taxane resistance.

  Study JGAS000370

• The single plasma-cell transcriptional landscape in POEMS syndrome

  POEMS syndrome is a rare monoclonal plasma cell disorder that shows unique symptoms distinct from other plasma cell neoplasms, including high levels of serum VEGF; however, none of the previous studies have succeeded in direct identification of plasma cell clones in POEMS syndrome, leaving their real nature obscure.���We herein performed single-cell RNA sequencing (scRNA-Seq) of bone marrow (BM) plasma cells from patients with POEMS syndrome. These data unveil unique features of POEMS clones among plasma cell neoplasms and enhance our understanding of the pathogenesis of POEMS syndrome.

  Study JGAS000289

• ChIP sequencing for β-catenin and histone modifications in HCC cell lines and organoids with CTNNB1 mutations

  CTNNB1 mutation is a major driver of HCC, particularly in metabolic-associated subtype. This study utilized patient-derived tumour organoids and cell lines harbouring various endogenous CTNNB1 mutations to comprehensively map the transcriptional repertoire regulated by mutant β-catenin through ChIP-seq under normal and fatty conditions. Genome-wide binding patterns of β-catenin were integrated with ChIP-seq data for histone modifications H3K27ac and H3K27me3 to assess active and repressive chromatin states. Oleic acid treatment was used to model fatty conditions.

  Study EGAS50000001274

• Contribution of specific cell types to the development of Barrett’s esophagus and carcinoma via germline genetic risk

  This study was designed to elucidate how individual cell types in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) contribute to disease development via germline genetic risk. We performed single cell RNA-sequencing (scRNA-seq) of BE, EAC and paired normal esophagus and gastric fundus tissue samples. After analyzing individual cell types, we integrated the scRNA-seq data and data of a genome-wide association study (GWAS) on BE/EAC to determine cell type-specific genetic risk. Raw data from the RNA-sequencing is provided here.

  Study EGAS50000000530

• Whole-genome methylation profiling of menstrual stem cells identifies novel biomarkers for endometriosis

  Endometriosis, despite its high prevalence, is underdiagnosed and poorly managed due to lack of clinically validated biomarkers and pathophysiological insight. Menstrual bloodderived stem cells (MenSCs) have been implicated in disease pathogenesis, but their diagnostic potential remains unexplored. We conducted a clinical study (n=42; 19 endometriosis, 23 controls) to assess whether DNA methylation profiles of freshly isolated MenSCs can identify disease-specific biomarkers. Whole-genome methylation sequencing revealed differentially methylated regions (DMRs) enriched in genes linked to hallmarks of endometriosis (e.g., inflammation, tissue remodelling, development). These DMRs robustly distinguished cases from controls, independent of technical and clinical variables. Machine learning models trained and validated on these DMRs achieved high diagnostic performance (specificity 83%, sensitivity 79%). Integration with an independent single-cell RNA sequencing dataset showed that the DMRs may modulate gene expression, further supporting their biological relevance. These findings position MenSC DNA methylation profiling as a promising, non-invasive approach for early endometriosis diagnosis and personalised care.

  Dataset EGAD50000002353

• Comparing sequencing of four proto-typical Burkitt lymphomas (BL) with IG-MYC translocation.

  By whole-genome, exome, transcriptome and methylome sequencing of four proto-typical Burkitt lymphomas (BL) with IG-MYC translocation we identified seven recurrently mutated genes including ID3. In an extended cohort, 36/53 (68%) molecularly-defined BL carried potentially damaging mutations of ID3 which were enriched at somatic hypermutation motifs. Only 6/47 (13%) other IG-MYC-positive B-cell lymphomas carried ID3 mutations suggesting cooperation of ID3 inactivation and IG-MYC translocation to be a hallmark of Burkitt lymphomagenesis.

  Study EGAS00001000271

• PROMETEO

  The SOLTI-1503 PROMETEO trial was a single-arm, preoperative, window-of-opportunity phase II study conducted at four sites in Spain between December 2018 and February 2022. It enrolled female patients with operable HER2-negative breast cancer (triple-negative or Luminal B-like) and residual disease after neoadjuvant chemotherapy. Tumor biopsies were collected at five time points (baseline, post-NAC screening, C2D1, C3D1, and surgery) for translational research. This dataset includes raw paired-end RNA sequencing data (~110M reads per library) generated from the 113 biopy samples, archived in FASTQ format.

  Study EGAS50000001499

• Genomic and Epigenomic Features of Primary and Recurrent Hepatocellular Carcinomas

  Intratumor heterogeneity and divergent clonal lineages within and among primary and recurrent hepatocellular carcinomas (HCCs) produce challenges to patient management. We investigated genetic and epigenetic variations within liver tumors, among hepatic lesions, and between primary and relapsing tumors. We performed whole-genome, whole-exome, or targeted capture sequencing analyses HCC specimens collected from multiple tumor regions and matched initial and recurrent tumors to obtain a systematic evaluation of intra- and intertumor genetic heterogeneity in HCC samples and to identify genetic changes associated with tumor progression and recurrence.

  Study EGAS00001002094

• Genomic Landscape of Malignant Peripheral Nerve Sheath Tumor-like Melanoma

  Malignant peripheral nerve sheath tumor (MPNST)-like melanoma is a rare malignancy with overlapping characteristics of both neural sarcoma and melanoma. The genomics of MPNST-like melanoma have not been previously described. This study provides the results of whole exome and transcriptome sequencing analysis of 8 samples from 6 patients with confirmed diagnosis of MPNST-like melanoma. This study demonstrates that MPNST-like melanoma shares oncogenic alterations common to both cutaneous melanoma and MPNST, and also suggests that MPNST-like melanoma harbors unique genomic and transcriptomic alterations.

  Study EGAS00001005065

• High-resolution lung adenocarcinoma expression subtypes identify tumors with dependencies on MET, CDK4, CDK6, and PD-L1

  Lung adenocarcinoma is one of the most common cancer types with various treatment modalities. However, better biomarkers to predict therapeutic response are still needed to improve precision medicine. We utilized a consensus hierarchical clustering approach on 509 LUAD cases from TCGA to identify five robust LUAD expression subtypes. We then integrated genomic (patient and cell line) and proteomic data to help define biomarkers of response to targeted therapies and immunotherapies. This approach defined subtypes with unique proteogenomic and dependency profiles.

  Study EGAS00001006461