{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"dataset_type":["N/A"],"full_dataset_link":["https://ega-archive.org/datasets/EGAD00001002652"],"sample_count":["284"],"description":["EGA dataset EGAD00001002652"],"repository":["EGA"],"title":["Deep sequencing of 60 genes from BCP HD ALL samples on Illumina HiSeq 2000, 100 bp paired-end"],"pubmed_abstract":["High hyperdiploidy defines the largest genetic entity of childhood acute lymphoblastic leukemia (ALL). Despite its relatively low recurrence risk, this subgroup generates a high proportion of relapses. The cause and origin of these relapses remains obscure. We therefore explored the mutational landscape in high hyperdiploid (HD) ALL with whole-exome (n=19) and subsequent targeted deep sequencing of 60 genes in 100 relapsing and 51 non-relapsing cases. We identified multiple clones at diagnosis that were primarily defined by a variety of mutations in receptor tyrosine kinase (RTK)/Ras pathway and chromatin-modifying genes. The relapse clones consisted of reappearing as well as new mutations, and overall contained more mutations. Although RTK/Ras pathway mutations were similarly frequent between diagnosis and relapse, both intergenic and intragenic heterogeneity was essentially lost at relapse. CREBBP mutations, however, increased from initially 18-30% at relapse, then commonly co-occurred with KRAS mutations (P<0.001) and these relapses appeared primarily early (P=0.012). Our results confirm the exceptional susceptibility of HD ALL to RTK/Ras pathway and CREBBP mutations, but, more importantly, suggest that mutant KRAS and CREBBP might cooperate and equip cells with the necessary capacity to evolve into a relapse-generating clone."],"pubmed_title":["KRAS and CREBBP mutations: a relapse-linked malicious liaison in childhood high hyperdiploid acute lymphoblastic leukemia."],"pubmed_authors":["Malinowska-Ozdowy K K, Frech C C, Schönegger A A, Eckert C C, Cazzaniga G G, Stanulla M M, zur Stadt U U, Mecklenbräuker A A, Schuster M M, Kneidinger D D, von Stackelberg A A, Locatelli F F, Schrappe M M, Horstmann M A MA, Attarbaschi A A, Bock C C, Mann G G, Haas O A OA, Panzer-Grümayer R R"],"additional_accession":[]},"is_claimable":false,"name":"GenePanel - samples","description":"50 ng of genomic double stranded DNA was enzymatically sheared to an average size of 200 bp. Further processing was performed using Illumina Nextera Rapid Capture Custom Kit (Illumina) and 100 bp paired-end sequencing was performed with 24 samples per lane on a Illumina HiSeq 2000 (Illumina) to reach a coverage of 100-1000x.","dates":{"updated":"2017-07-26 15:39:28"},"accession":"EGAD00001002652","cross_references":{"TAXONOMY":["9606"],"pubmed":["25917266"],"EGA":["EGAC00001000262","EGAS00001001113"]}}