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• Whole genome and transcriptome analysis of a sporadic and recurring parathyroid carcinoma

  Parathyroid carcinoma is an extremely rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion of parathyroid hormone, extremely high serum calcium level and the deleterious effects of hypercalcemia are the clinical manifestations of the disease. Up to 60% of patients develop multiple disease recurrences and although long-term survival is possible with palliative surgery, permanent remission is rarely achieved. Molecular drivers of sporadic parathyroid carcinoma have remained largely unknown. Previous studies, mostly based on familial cases of the disease, suggested a potential role for the tumor suppressor MEN1 and proto-oncogene RET in benign parathyroid tumorigenesis while the tumor suppressor HRPT2 and proto-oncogene CCND1 may also act as drivers in parathyroid cancer. Here, we report the complete genomic analysis of a sporadic and recurring parathyroid carcinoma. Mutational landscapes of the primary and recurrent tumor specimens were analyzed using high throughput sequencing technologies. Such molecular profiling allowed for identification of somatic mutations never previously identified in this malignancy. These included single nucleotide point mutations in well characterized cancer genes such as mTOR, MLL2, CDKN2C and PIK3CA. Comparison of acquired mutations in patient-matched primary and recurrent tumors revealed loss of PIK3CA activating mutation during the evolution of the tumor from the primary to the recurrence. Structural variations leading to gene fusions and regions of copy loss and gain were identified at a single-base resolution. Loss of short arm of chromosome 1 along with somatic mis-sense and truncating mutations in CDKN2C and THRAP3, respectively, provide new evidence for the potential role of these genes as tumor suppressors in parathyroid cancer. The key somatic mutations indentified in this study can serve as novel diagnostic markers as well as therapeutic targets.

  Study EGAS00001000484

• Whole genome sequencing of pancreatic cystic fluid for early detection and diagnosis of pancreatic cancer

  Pancreatic cancer (PC) is a leading cause of cancer-related deaths globally. Accurate PC detection at early or premalignant stage, when surgery is effective, would increase survival rates and prevent unnecessary surgery or surveillance. Molecular diagnostic attempts using PCy fluid (PCyF), as a liquid biopsy, to analyze common mutations associated with PC development are yet to contribute to early diagnosis. Whole genome sequencing (WGS) is utilized in various cancers, PC inclusive, for detecting genetic changes associated with carcinogenesis, but not in PCyF due to technical limitations, including isolated DNA purity. The goal of the study was to achieve high quality of WGS from PCyF from 9 patients to enable development of signatures of malignancy. The WGS was performed using Illumina sequencing. Experimental design was at a 50x depth.

  Dataset EGAD50000000869

• Identification of drug resistance genes in melanoma

  Our aim is to analyze the genome of human melanoma cell lines and short term culture from human melanoma samples in order to identify genes that confer drug resistance to clinically relevant targeted therapies. We will perform whole-exome sequencing, copy number variation analysis and methylome analysis in a collection of human melanoma cell lines and short term culture that will be then screened for drug sensitivity/resistance through a library of clinically relevant drugs and drug combinations. By the combined analysis of the genomic lesion and the drug sensitivity/resistance profile of different cell lines, we will look for genes whose mutation is associated to the sensitivity or resistance to a specific drug in different samples.

  Dataset EGAD00001001124

• Investigating Human Placentation and Pregnancy Using First Trimester Chorionic Villi

  Chorionic villus sampling (CVS) is routinely used for prenatal diagnosis of cytogenetic disorders, but also possesses great potential for studying placentation. To better understand villi biology, human placentation, and how these relate to pregnancy outcomes, we examined the morphology and transcriptomes of villi obtained via CVS from 10-14 weeks of pregnancy and correlated these with pregnancy attributes and clinical outcomes.

  Study phs001320

• Transcriptome sequencing of Gingivo-buccal Cancer : ICGC-India Project_YR03

  Transcriptome Sequencing of Gingivo-buccal Cancer: ICGC-India ProjectAs a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India. There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection. Transcriptome sequencing of paired RNA samples – isolated from the tumor and adjacent normal tissues of 12 patients – have been performed. Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from adjacent normal and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai. Sequencing is being performed at the National Institute of Biomedical Genomics, Kalyani.

  Study EGAS00001002851

• Transcriptome sequencing of Gingivo-buccal Cancer : ICGC-India Project_Batch05

  Transcriptome Sequencing of Gingivo-buccal Cancer: ICGC-India ProjectAs a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India. There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection. Transcriptome sequencing of paired RNA samples – isolated from the tumor and adjacent normal tissues of 28 patients – have been performed. Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from adjacent normal and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai. Sequencing is being performed at the National Institute of Biomedical Genomics, Kalyani.

  Study EGAS00001003285

• Whole genome sequencing data of pediatric hypodiploid acute lymphoblastic leukemia

  Hypodiploid acute lymphoblastic leukemia (ALL) is a rare subtype of B-cell ALL characterized by chromosome number < 45 , encompassing near-haploid (24–29 chromosomes) and low-hypodiploid (30–39 chromosomes) subgroups. These subgroups display distinct genetic landscapes, including Ras and receptor tyrosine kinase pathway alterations in near-haploid ALL, and frequent IKZF2, RB1, and germline TP53 alterations in low-hypodiploid ALL. Clinically, hypodiploid ALL is associated with dismal prognosis, with 5-year overall survival rates often between 50-70% in children and markedly worse in adults. Despite advances in risk stratification and MRD-guided therapy, allogeneic stem cell transplantation remains the current standard recommendation for affected patients.

  Study EGAS50000001305

• RNA sequencing data of pediatric hypodiploid acute lymphoblastic leukemia

  Hypodiploid acute lymphoblastic leukemia (ALL) is a rare subtype of B-cell ALL characterized by chromosome number < 45 , encompassing near-haploid (24–29 chromosomes) and low-hypodiploid (30–39 chromosomes) subgroups. These subgroups display distinct genetic landscapes, including Ras and receptor tyrosine kinase pathway alterations in near-haploid ALL, and frequent IKZF2, RB1, and germline TP53 alterations in low-hypodiploid ALL. Clinically, hypodiploid ALL is associated with dismal prognosis, with 5-year overall survival rates often between 50-70% in children and markedly worse in adults. Despite advances in risk stratification and MRD-guided therapy, allogeneic stem cell transplantation remains the current standard recommendation for affected patients.

  Study EGAS50000001806

• Gut metagenome/FINRISK 2002 (Salosensaari et al. Nature Comms 2021)

  The main goal of the project is the study the associations between the gut metagenome and human health. The dataset contains data for n=7211 FINRISK 2002 participants who underwent fecal sampling. Demultiplexed shallow shotgun metagenomic sequences were quality filtered and adapter trimmed using Atropos (Didion et al., 2017), and human filtered using Bowtie2 (Langmead and Salzberg, 2012).

  Study EGAS00001005020

• 5- FU treated organoids

  5-Fluorouracil (5-FU) is a chemotherapeutic drug component that is commonly used for the treatment of solid cancers. The anticancer properties of 5-FU have been attributed to interference with nucleotide synthesis and through direct incorporation into the DNA as being a pyrimidine analog. As both mechanisms of action may have a mutational impact on surviving tumor cells, we performed three independent analyses to characterize the genomic consequences of 5-FU treatment: i) in vitro treatment of intestinal organoids with 5-FU followed by whole genome sequencing, ii) genome-wide mutation analyses in tumor samples from 5-FU treated patients with breast or colorectal cancer, and iii) analysis of paired biopsies from patients treated with 5-FU between biopsies. Our results demonstrate that both in vitro and in vivo 5-FU causes a mutational pattern that is dominated by T&gt;G substitutions in a CTT context and with strong resemblance to COSMIC signature 17. Interestingly, this signature is also found in non 5-FU treated patients, most prominently in esophageal tumors, indicating that distinct endogenous and exogenous triggers can converge into highly similar mutational signatures. Furthermore, our results suggest that 5-FU may have adverse mutagenic effects on healthy cells and contributes to genetic variability in surviving cancer cells thereby contributing to tumor evolution.

  Study EGAS00001003592