Project description:Prostate cancer is the most common malignancy in men. Yet, the modest benefit of treatment highlights the unmet need for prognostic biomarkers in prostate cancer (1). Few large prostate oncogenome resources currently exist that combine the molecular and clinical outcome data necessary for prognostic discovery. To determine the extent to which genomic aberrations reflect the risk of prostate cancer-specific outcomes, we profiled more than 100 primary prostate cancers with long-term follow-up for genome-wide copy number alterations (CNA). We also updated the long-term clinical outcome (median 8 years) of an additional independent cohort of 181 primary prostate cancers that we previously profiled for CNA and expression changes (2). Together, we found that CNA burden across the genome, defined as the percent of the tumor genome affected by CNA, is prognostic for recurrence and metastasis in these two cohorts. This prognostic significance of CNA is independent of Gleason grade, a major existing histopathological prognostic variable in prostate cancer. Moreover, in intermediate-risk Gleason 7 prostate cancers that show a wide range of outcomes, CNA burden is also prognostic for biochemical recurrence, independent of prostate-specific antigen or nomogram score. CNA burden therefore has the potential to stratify patients by their risk of recurrence in an otherwise intermediate risk subpopulation. We further demonstrate that CNA burden can be established in diagnostic FFPE needle biopsies using low-input whole genome sequencing. Together, this work highlights the potential of oncogenomics to identify useful and clinically amenable prognostic factors that may inform prostate cancer outcome and treatment. Human prostate samples were profiled on Agilent 1M aCGH arrays per manufacturer's instructions. A pooled reference normal DNA was used as the reference.
Project description:Copy number alteration (CNA) is a good signpost to identify cancer related genes. CNAs were analyzed using the Agilent 244K array comparative genomic hybridization (aCGH) in fresh-frozen tumor and matched normal tissues from 10 gastric cancer patients.
Project description:Copy number alteration (CNA) is a good signpost to identify cancer related genes. CNAs were analyzed using the Agilent 400K array comparative genomic hybridization (aCGH) in fresh-frozen tumor and matched normal tissues from 30 gastric cancer patients.
Project description:Advanced prostate cancer is a highly heterogenous disease with few in vitro models. We report generation of seven novel 3D organoid lines of patient-derived prostate cancer. We determine the copy number alterations of these lines using array CGH. They contain may classic alterations of prostate cancer such as lost of the short arm of chromosome 8 and gain of the long arm of chromosome 8. In addition, we found homozygous deleteion of tumor suppressor PTEN and CHD1 as well as the TMPRSS2-ERG interstitial deletion. Prostate cancer organoid lines, ~2 months after in vitro propagation, were used for profiling on Agilent 1M aCGH arrays per manufacturer's instructions. A pooled reference normal DNA was used as the reference.
Project description:Copy number alteration (CNA) is a good signpost to identify cancer related genes. CNAs were analyzed using the Agilent 400K array comparative genomic hybridization (aCGH) in fresh-frozen tumor and matched normal tissues from 30 gastric cancer patients. Whole genomic CNAs in 30 human gastric cancers were analyzed using the Agilent aCGH-400K arrays. Matched normal tissues were used as the reference.
Project description:The level of copy number alteration (CNA), or CNA burden, in cancer genomes is associated with recurrence and metastasis in prostate cancer. As clinical genomic analysis of tumors and tumor biopsies becomes widespread, there is a growing need to understand the prognostic factors captured by genomic features, especially in prostate cancer where conservative treatment approaches are increasingly common. Here we analyze the CNA landscape of conservatively treated prostate cancer in a prostate cancer biopsy and transurethral resection cohort. We find that CNA burden is prognostic for metastasis and cancer-specific survival, independent of clinical prognostic factors such as Gleason and CAPRA score, in conservatively treated prostate cancer.
Project description:Copy number profiling of 1000 Genomes Phase 3 inidividuals using the Agilent 1M aCGH arrays Two color experiment. NA10851 used as reference against 2534 other individuals from the phase 3 of the 1000 Genomes project