DAC

DKFZ-HIPO Data Access Committee of Heidelberg Center for Personalized Oncology

Dac ID Contact Person Email Access Information
EGAC00001000452 Katja Beck k [dot] beck [at] dkfz [dot] de No additional information is available

This DAC controls 22 datasets:

Dataset ID Description Technology Samples
EGAD00001001444 Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants and young children. Although the prognosis of ATRT patients is poor, some patients respond very well to current treatments, suggesting inter-tumor molecular heterogeneity. To investigate this further, we genetically and epigenetically analyzed a large cohort of ATRTs (n = 170). Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location and type of SMARCB1 alterations, were identified using DNA-methylation or gene expression analyses. Whole genome DNA- and RNA-sequencing found no other recurrent mutations explaining the differences between subgroups. However, whole genome bisulfite-sequencing and H3K27Ac ChIP-sequencing of primary tumors revealed clear differences in methylation patterns and enhancer landscapes, leading to the identification of subgroup-specific regulatory networks. Illumina HiSeq 2000;, Illumina HiSeq 2500; 55
EGAD00001000997 Whole-exome sequencing of a chronic lymphocytic leukemia (CLL) developed during vemurafenib treatment of a patient with malignant melanoma. Peripheral blood mononuclear cells were separated by Ficoll gradient centrifugation. DNA was extracted from highly purified (>97%) CD19+CD5+ cells obtained from the patient while being under BRAF inhibition versus CD14+ germline control cells (>90% purity). No alterations that could be linked to aberrant RAS activity or paradoxical RAF/MEK/ERK signaling could be identified in the CLL, which shows characteristic copy number alterations. Illumina HiSeq 2500; 2
EGAD00001002528 WGS from EGAS00001001857 Illumina HiSeq 2000; 18
EGAD00001000995 HIPO blastemal Wilms (nephroblastoma) characterisation of tumor driving DNA alterations Illumina HiSeq 2000; 112
EGAD00001000992 HIPO blastemal Wilms (nephroblastoma) characterisation of tumor driving events caused by differential SIX1 binding of the SIX1 Q177R mutatns Illumina HiSeq 2500; 3
EGAD00001001384 Mutations that activate the RAF-MEK-ERK signaling pathway, in particular BRAFV600E, occur in many cancers, and mutant BRAF-selective inhibitors have clinical activity in these diseases. Activating BRAF alleles are usually considered to be mutually exclusive with mutant RAS, whereas inactivating mutations in the D594F595G596 motif of the BRAF activation segment can coexist with oncogenic RAS and cooperate via paradoxical MEK/ERK activation. We determined the functional consequences of a largely uncharacterized BRAF mutation, F595L, which was detected along with an HRASQ61R allele by clinical exome sequencing in a patient with histiocytic sarcoma and also occurs in epithelial cancers, melanoma, and neuroblastoma, and investigated its interaction with mutant RAS. We demonstrate that, unlike previously described DFG motif mutants, BRAFF595L is a gain-of-function variant with intermediate activity towards MEK that does not act paradoxically, but nevertheless cooperates with mutant RAS to promote oncogenic signaling. Of immediate clinical relevance, BRAFF595L shows divergent responses to different mutant BRAF-selective inhibitors, whereas signaling driven by BRAFF595L with and without mutant RAS is efficiently blocked by pan-RAF and MEK inhibitors. Mutation data from primary patient samples and cell lines show that BRAFF595L, as well as other BRAF mutations with intermediate activity, frequently coincide with mutant RAS in a broad spectrum of cancers. These data define a novel class of activating BRAF mutations that cooperate with oncogenic RAS in a non-paradoxical fashion to achieve an optimal level of MEK-ERK signaling, extend the spectrum of patients with systemic histiocytic disorders and other malignancies who are candidates for therapeutic blockade of the RAF-MEK-ERK pathway, and underscore the value of comprehensive genetic profiling for understanding the signaling requirements of individual cancers. Illumina HiSeq 2500; 2
EGAD00001002159 Exome Seq for Study EGAS00001001844 Illumina HiSeq 2000; 2
EGAD00001002161 Transcriptome from EGAS00001001845 Illumina HiSeq 2500; 1
EGAD00001002160 Exome Seq for EGAS00001001845 Illumina HiSeq 2500; 2
EGAD00001002162 Exome Seq from EGAS00001001846 Illumina HiSeq 2500; 2
EGAD00001000884 In order to elucidate whether newly acquired genetic alterations during serial transplantation of patient derived primary pancreatic cancer cultures contribute to the observed clonal dynamics in vivo, all coding genes of two patient derived primary cultures and derived genetically marked serial xenografts (1°/2°/3°) were sequenced. Illumina HiSeq 2000; 10
EGAD00001000993 HIPO blastemal Wilms (nephroblastoma) characterisation of tumor driving gene expression events Illumina HiSeq 2000; 40
EGAD00001000994 HIPO blastemal Wilms (nephroblastoma) characterisation of tumor driving chromosomal aberrations Illumina HiSeq 2000;, Illumina HiSeq 2500; 56
EGAD00001002011 RNA sequencing data of whole blood samples from smoking and non-smoking mothers and their children at gestation/birth and follow-up years. 64
EGAD00001002012 ChIPseq data of whole blood samples from smoking and non-smoking mothers and their children at gestation/birth and follow-up years. 16
EGAD00001002138 WGS data of Atypical teratoid/rhabdoid tumors (ATRT) Illumina HiSeq 2000; 36
EGAD00001002135 ChIPseq data of Atypical teratoid/rhabdoid tumors (ATRT) Illumina HiSeq 2000;, Illumina HiSeq 2500; 15
EGAD00001002137 WGBS data of Atypical teratoid/rhabdoid tumors (ATRT) Illumina HiSeq 2000; 15
EGAD00001002136 RNA sequencing data of Atypical teratoid/rhabdoid tumors (ATRT) Illumina HiSeq 2000; 25
EGAD00001000366 WGBS data of whole blood samples from smoking and non-smoking mothers and their children at gestation/birth and follow-up years. Illumina HiSeq 2000; 52
EGAD00001002163 Transcriptome from EGAS00001001846 Illumina HiSeq 2500; 1
EGAD00001002164 Exome from EGA00001001848 Illumina HiSeq 2000; 2