DAC

PanCuRx Data Access Committee, Ontario Institute for Cancer Research

Dac ID Contact Person Email Access Information
EGAC00001000710 Julie Wilson oicr-dac [at] oicr [dot] on [dot] ca No additional information is available

This DAC controls 14 datasets:

Dataset ID Description Technology Samples
EGAD00001003582 Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer - Early Results from the COMPASS Trial - RNA-Seq unmapped reads Illumina HiSeq 2500 50
EGAD00001003584 Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer - Early Results from the COMPASS Trial - RNA-Seq mapped reads 0
EGAD00001003585 Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer - Early Results from the COMPASS Trial - WGS mapped reads 0
EGAD00001003586 Whole Genomes Define Concordance in Matched Primary, Xenograft, and Organoid Models of Pancreas Cancer - WGS mapped reads 54
EGAD00001004548 Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases - RNA-Seq mapped and unmapped reads Illumina HiSeq 2500 75
EGAD00001004551 Integration of Genomic and Transcriptional Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases - WGS mapped reads 0
EGAD00001005799 Bam and fastq files from RNA-seq of PDAC samples described in Transcription phenotypes of pancreatic cancer are driven by genomic events events during tumour evolution Illumina HiSeq 2500,unspecified 34
EGAD00001006081 PURPOSE: To determine the impact of basal-like and classical subtypes in advanced PDAC and to explore GATA6 expression as a surrogate biomarker. EXPERIMENTAL DESIGN: Within the COMPASS trial patients proceeding to chemotherapy for advanced PDAC undergo tumour biopsy for RNA sequencing. Overall response rate (ORR) and overall survival (OS) were stratified by subtypes and according to chemotherapy received. Correlation of GATA6 with the subtypes using gene expression profiling, in situ hybridization (ISH) were explored. RESULTS: Between December 2015-May 2019, 195 patients (95%) had enough tissue for RNA sequencing; 39 (20%) were classified as basal-like and 156 (80%) as classical. RECIST response data were available for 157 patients; 29 basal-like and 128 classical where the ORR was 10% vs. 33% respectively (p=0.02). In patients with basal-like tumours treated with modified FOLFIRINOX (mFFX) (n=22) the progression rate was 60% compared to 15% in classical PDAC (p= 0.0002). Median OS in the intention to treat population (n=195) was 9.3 months for classical vs. 5.9 months for basal-like PDAC (HR 0.47 95% CI 0.32-0.69, p=0.0001). GATA6 expression by RNAseq highly correlated with the classifier (p<0.001) and ISH predicted the subtypes with sensitivity of 89% and specificity of 83%. In a multivariable analysis, GATA6 expression was prognostic (p=0.02). In exploratory analyses, basal-like tumours, could be identified by keratin 5, were more hypoxic and enriched for a T cell inflamed gene expression signature. CONCLUSIONS: The basal-like subtype is chemoresistant and can be distinguished from classical PDAC by GATA6 expression. Illumina HiSeq 2500,unspecified 101
EGAD00001006152 Bam files from WGS of PDAC samples described in: Transcription phenotypes of pancreatic cancer are driven by genomic events events during tumour evolution 0
EGAD00001006261 Bam and fastq files from RNA-seq of PDAC samples used in the PCSI mismatch repair study Illumina HiSeq 2500,unspecified 4
EGAD00001006262 Bam files from WGS of PDAC samples used in the PCSI mismatch repair study 0
EGAD00001007571 Background and Aims: Homologous recombination deficiency (HRD) in pancreatic ductal adenocarcinoma (PDAC), remains poorly defined beyond germline(g) alterations in BRCA1, BRCA2 and PALB2. Methods: We interrogated whole genome sequencing (WGS) data on 391 patients including 49 carriers of pathogenic variants (PVs) in g_BRCA_ and PALB2. HRD classifiers were applied to the dataset and included: 1) the genomic instability score (GIS) used by Myriad MyChoice HRD assay; 2) substitution base signature 3 (SBS3); 3) HRDetect; and, 4) Structural Variant (SV) burden. Clinical outcomes and responses to chemotherapy were correlated with HRD status. Results: Biallelic tumour inactivation of g_BRCA_ or PALB2 was evident in 43/49 germline carriers identifying HRD-PDAC. HRDetect (score ?0.7) predicted gBRCA1/PALB2 deficiency with highest sensitivity (98%) and specificity (100%). HRD genomic tumour classifiers suggested that 7-10% of PDAC that do not harbor g_BRCA/PALB2_ have features of HRD. Of the somatic HRDetect cases, 69% were attributed to alterations in BRCA1/2, PALB2, RAD51C/D and XRCC2, and a tandem duplicator phenotype. TP53 loss was more common in BRCA1- compared to BRCA2-associated HRD-PDAC. HRD status was not prognostic in resected PDAC. However in advanced disease the GIS (p=0.02), SBS3 (p=0.03) and HRDetect score (p=0.005) were predictive of platinum response and superior survival. PVs in g_ATM_ (n=6) or g_CHEK2_ (n=2) did not result in HRD-PDAC by any of the classifiers. In four patients, BRCA2 reversion mutations associated with platinum resistance. Conclusions: Germline and parallel somatic profiling of PDAC outperforms germline testing alone in identifying HRD-PDAC. An additional 7-10% of patients without gBRCA/PALB2 mutations may benefit from DNA damage response agents. 0
EGAD00001008155 Intratumoral heterogeneity is a critical frontier in understanding how the tumor microenvironment (TME) propels malignant progression. Here, we deconvolute the human pancreatic TME through large-scale integration of histology-guided regional multiOMICs with clinical data and patient-derived preclinical models. We discover subTMEs, histologically definable tissue states anchored in fibroblast plasticity, with regional relationships to tumor immunity, subtypes, differentiation, and treatment response. Reactive subTMEs rich in complex but functionally coordinated fibroblast communities were immune-hot and inhabited by aggressive tumor cell phenotypes. The matrix-rich deserted subTMEs harbored less activated fibroblasts and tumor- suppressive features yet were markedly chemoprotective and enriched upon chemotherapy. SubTMEs originated in fibroblast differentiation trajectories and transitory states were notable both in single cell transcriptomics and in situ. The intratumoral co-occurrence of subTMEs produced patient-specific phenotypic and computationally predictable heterogeneity tightly linked to malignant biology. Therefore, heterogeneity within the plentiful, notorious pancreatic TME is not random but marks fundamental tissue organizational units. Illumina HiSeq 2500,unspecified 29
EGAD00010001811 h5 files from 15 single cell PDAC samples described in "Transcription phenotypes of pancreatic cancer are driven by genomic events events during tumour evolution" 15