Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma.
Katrin S KurzKortine KleinheinzSietse M AukemaMarius RohdeStephan H BernhartDaniel HübschmannRabea WagenerUmut H ToprakFrancesco RaimondiMarkus KreuzSebastian M WaszakZhiqin HuangLina SieverlingNagarajan ParamasivamJulian SeufertStephanie SungaleeRobert B RussellJulia BausingerHelene KretzmerOle AmmerpohlAnke K BergmannHans BinderArndt BorkhardtBenedikt BrorsAlexander ClaviezGero DooseLars FeuerbachAndrea HaakeMartin-Leo HansmannJessica HoellMichael HummelJan O KorbelChris LawerenzDido LenzeBernhard RadlwimmerJulia RichterPhilip RosenstielAndreas RosenwaldMarkus B SchilhabelHarald SteinStephan StilgenbauerPeter F StadlerMonika SzczepanowskiMarc A WenigerMarc ZapatkaRoland EilsPeter LichterMarkus LoefflerPeter MöllerLorenz TrümperWolfram Klappernull nullSteve HoffmannRalf KüppersBirgit BurkhardtMatthias SchlesnerReiner SiebertPublished in: Nature communications (2019)
Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.
Keyphrases
- single cell
- diffuse large b cell lymphoma
- transcription factor
- copy number
- genome wide
- rna seq
- late onset
- gene expression
- papillary thyroid
- young adults
- high resolution
- amyotrophic lateral sclerosis
- dna methylation
- squamous cell carcinoma
- dna repair
- squamous cell
- early onset
- high density
- mass spectrometry
- lymph node metastasis