Project description:This SuperSeries is composed of the following subset Series: GSE21948: High Density custom Agilent 44K CGH array analysis of 7q and TET2 region in myelodysplastic/myeloproliferative neoplasms GSE21990: Affymetrix SNP 6.0 array data for myelodysplastic/myeloproliferative neoplasms Refer to individual Series
Project description:Tumour initiation begins with a single oncogenic mutation within a single cell, leading to hyperproliferation and clonal expansion. These mutant preneoplastic cells may undergo various fates such as: death, dormancy, benign growth or malignant growth. Whilst further genetic mutations have been linked to progression of preneoplastic cells, even genetically identical preneoplastic cells may undergo different fates. To better understand the phenotypic heterogeneity between genetically identical preneoplastic cells during tumour initiation we have performed single-cell RNA sequencing on preneoplastic cells derived from an inducible larval zebrafish model of skin cancer. Furthermore, inflammation has been identified as a potent driving force in oncogenesis. Macrophages have especially been shown to promote cancer cell growth and progression, whilst neutrophils have the potential to perform either pro- or anti-tumour functions. To study the first responses of myeloid cells following initial oncogenic transformation we also profiled sorted myeloid cells at the single cell level.
Project description:Pancreatic neuroendocrine neoplasms (PNENs) are biologically and clinically heterogeneous neoplasms. We used quantitative global proteomic analysis on 40 PNENs to compliment paired transcriptome data.
Project description:Transcriptomic profiling of Ras/Src tumours from animals raised on CD versus HSD enabled the identification of (i) candidate tumour-derived factors which may impact muscle-wasting and (ii) candidate amino acid transporters which may impact tumor growth.
Project description:Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-Box helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. Moreover, corresponding deletions on 5q35.3 present in 6% of cases lead to haploinsufficient DDX41 expression. DDX41 lesions caused altered pre-mRNA splicing and RNA processing. DDX41 is exemplary of other RNA helicase genes also affected by somatic mutations, suggesting that they constitute a family of tumor suppressor genes. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples.
Project description:Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-Box helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. Moreover, corresponding deletions on 5q35.3 present in 6% of cases lead to haploinsufficient DDX41 expression. DDX41 lesions caused altered pre-mRNA splicing and RNA processing. DDX41 is exemplary of other RNA helicase genes also affected by somatic mutations, suggesting that they constitute a family of tumor suppressor genes.
Project description:To investigate which factors might be driving the cachectic muscle wasting observed in our larval models bearing RasV12, scrib1 tumors, we performed RNA sequencing (RNAseq) on the cuticles of wild type and RasV12, scrib1 tumour-bearing larvae. Pathway and gene ontology analysis revealed significant deregulation of stress and starvation response genes, metabolic genes, and inflammation and immune regulatory genes within cachectic muscle of tumour bearing larvae.