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• Genetic subtyping by Whole Exome Sequencing across Diffuse Large B Cell Lymphoma and Plasmablastic Lymphoma.

  99 FFPE derived tumor tissue DNA, 9 circulating tumor DNA samples and 38 paired germline DNA were used. A library containing whole exome regions was used to isolate the DNA for sequencing (SureSelect XT Human All Exon V6 (Agilent technologies)). Sequencing on a NovaSeq 6000 instrument (Illumina, paired end, 2x100, mean 566Gb per FlowCell) at the National Genomic Analysis Center (CNAG, Barcelona, Spain) was performed.

  Study EGAS50000000371

• Multi-omics analysis reveals immune programs delineating disease severity in extrapulmonary tuberculosis

  This study investigates the immune response in extrapulmonary tuberculosis (EPTB) using a combination of bulk and single-cell RNA sequencing. Hierarchical clustering of patient transcriptomes identified three distinct levels of disease severity, uncovering immunological pathways involved in disease progression, including interferon and IL-1β-mediated signaling. The findings also led to the development of a diagnostic gene expression signature for both EPTB and pulmonary TB, offering potential improvements in TB diagnosis and treatment.

  Study EGAS50000000668

• Distinct genomic profile and specific targeted drug responses in adult cerebellar glioblastoma

  Only a few studies have reported the molecular characteristics of adult cerebellar glioblastoma (C-GBM), a subtype comprising 1% of glioblastoma cases located within the infratentorial brain region due to the rarity. By identifying genomic profiles from 19 adult C-GBM samples, we revealed the genetic intertumoral heterogeneity in C-GBM as well as distinct genomic characteristics from those of supratentorial glioblastomas (S-GBMs), emphasizing the need of individualized therapies for C-GBM patients.

  Study EGAS00001002517

• Variant calling analysis of cfDNA whole exome sequencing in neuroblastoma

  This dataset contains VCF files from a variant calling analysis of 19 neuroblastoma patients. WES or WGS data of the primary tumor were compared to WES cfDNA analysis at the time of diagnosis and at a 2nd timepoint (complete remission, partial remission, disease progression or relapse). For 4 patients, WGS of germline, tumor at diagnosis and tumor at relapse DNA was performed on Illumina HiSeq2500, with 100-bp paired-end reads. For the other patients, WES was performed using either an AgilentSureSelect Human All Exon v5 or a Roche Nimblegen SeqCap EZ Exome V3 kit on Illumina HiSeq2000, with 100-bp paired-end reads. SNVs observed in any of the primary tumors or cfDNA samples studied by WES were targeted using a capture sequencing panel at all intermediate time points.

  Dataset EGAD00001003803

• Targeted sequencing of paired tumour/blood of 34 T1 stage bladder cancer patients

  Stage T1 bladder cancer presents a high risk of progression and requires improved understanding. In continuation of our whole-exome sequencing study on this subtype of the disease, we carried out this targeted paired tumour/blood sequencing study including 34 T1 stage bladder cancer patients. Agilent’s SureDesign tool was used to design a 1.133 Mb SureSelect custom capture for all coding exons of the 140 selected candidate genes.

  Study EGAS00001005767

• Clinical utility of combined low-pass whole genome and targeted sequencing in liquid biopsies for diagnosis and monitoring of pediatric solid tumors

  We designed a liquid biopsy (LB) platform employing Low-Pass Whole Genome Sequencing (LP-WGS) and targeted sequencing of cell-free (cf) DNA isolated from plasma for detecting genome-wide copy number alterations and targeted gene fusions in pediatric solid tumors. A total of 143 plasma samples were analyzed from 19 controls (patients with non-oncologic diagnoses) and 73 patients, including 44 with bone or soft tissue sarcomas, 12 with renal tumors, 10 with germ cell tumors, 5 with hepatic tumors, and 2 with thyroid tumors.

  Study EGAS00001006913

• Plasma MicroRNA Signatures of Aging

  Background. MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally and show differential expression in various tissues with aging phenotypes. Detectable in circulation, extracellular microRNAs reflect (patho)physiological processes and hold promise as biomarkers for healthy aging and age-related diseases. This study aimed to explore plasma extracellular microRNAs as biological aging indicator and their associations with health outcomes using population-level data. Methods. We quantified plasma expression levels of 2,083 extracellular microRNAs using targeted RNA-sequencing in 2,684 participants from the population-based Rotterdam Study cohort. The training and test sets included 1,930 participants from the advanced-aged initial and second subcohort (RS-I/RS-II; median age: 70.6), while the validation set comprised 754 participants from the middle-aged fourth subcohort (RS-IV; median age: 53.5). Based on 591 microRNAs well-expressed in plasma, we examined differential expression of microRNAs with chronological age, PhenoAge –a composite score of age and nine multi-system blood biomarkers–, the frailty index, and mortality. Next, elastic net models were employed to construct composite microRNA-based aging biomarkers predicting chronological age (mirAge), PhenoAge (mirPA), frailty index (mirFI), and mortality (mirMort). The association of these aging biomarkers with different age-related health outcomes was assessed using Cox Proportional Hazard, linear regression, and logistic regression models in the test and validation sets. Results. We identified 188 microRNAs differentially expressed with chronological age within the RS-I/RS-II advanced-aged population (ntraining=1158, ntest=772), of which 177 microRNAs (94.1%) were replicated in the middle-aged RS-IV subcohort (nvalidation=754). Moreover, 227 miRNAs showed robust associations with PhenoAge, 61 with FI, and 16 with ten-year mortality independent of chronological age. Subsequently, we constructed four plasma microRNA-based aging biomarkers: mirAge with 108, mirPA with 153, mirFI with 81, and mirMort with 50 miRNAs. Elevated scores on these microRNA-based aging biomarkers were associated with unfavorable health outcomes, including lower subjective physical functioning and self-reported health and increased mortality and frailty risk, but not with first- or multi-morbidity. Overall, larger effect estimates were observed for mirPA, mirFI, and mirMort compared to mirAge. Conclusions. This study describes distinct plasma microRNA-aging signatures and introduces four microRNA-based aging biomarkers with potential to identify accelerated aging and age-related decline, providing insights into the intricate process of human aging.

  Study EGAS00001008117

• A machine learning classifier for DNA repair defects using plasma DNA

  Study EGAS00001007006

• The Genomic Landscape of Interval Colorectal Cancers

  Interval colorectal cancers (CRC), cancers diagnosed after a screening/surveillance exam in which no cancer is detected, and before the date of the next recommended exam, reflect an unprecedented challenge in CRC detection and prevention. To better understand this poorly characterized CRC variant, we examined the clinical and mutational characteristics of interval CRCs in comparison to screen-detected CRCs. We used data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer randomized controlled trial (RCT) of flexible sigmoidoscopy (FS) screening, which enrolled 154,900 men and women aged 55 to 74 years between 1993 and 2001. Whole Exome Sequencing (WES) was performed on 323 samples from 168 participants (data available through dbGaP). We found colorectal cancers diagnosed between screening exams (interval cancers) had significantly increased risk of death than screen detected cancers although no significant molecular differences were observed between screen-detected and interval CRC at the whole exome sequencing level.

  Study phs003093

• High-grade B-cell lymphoma, not otherwise specified: an LLMPP study

  Molecular characterization of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS), is hindered by its rarity, evolving definition, and poor diagnostic reproducibility. To address this challenge, we analyzed 92 HGBCL-NOS tumors collected across Lymphoma/Leukemia Molecular Profiling Project sites. These tumors were profiled using whole-genome sequencing (WGS) or whole-exome sequencing (WES) to identify somatic mutations, WGS or low-pass WGS to detect copy number alterations, targeted capture sequencing to assess MYC and BCL2 structural variants, and RNA sequencing. The genetic features of HGBCL-NOS were compared to those of diffuse large B-cell lymphoma (DLBCL-NOS) and EBV-negative adult Burkitt lymphoma (BL). DLBCL-NOS tumors underwent targeted capture sequencing using a panel of 125 genes recurrently mutated in aggressive B-cell lymphomas. BL biopsies were drawn from the Burkitt Lymphoma Genome Sequencing Project and had available WGS (dbGaP Study Accession: phs000527.v18.p6).

  Study EGAS50000000932