Integrated genomic analyses of ovarian carcinoma.

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients' lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.

Usage

data( TCGA.RNASeqV2_eset )

Format

experimentData(eset):
Experiment data
  Experimenter name: Integrated genomic analyses of ovarian carcinoma. Nature 2011, 474:609-615.
  Laboratory: Cancer Genome Atlas Research Network 2011
  Contact information:
  Title: Integrated genomic analyses of ovarian carcinoma.
  URL:
  PMIDs: 21720365

  Abstract: A 179 word abstract is available. Use 'abstract' method.
  Information is available on: preprocessing
  notes:
   platform_title:
      [RNASeqV2] Illumina HiSeq RNA sequencing
   platform_shorttitle:
      Illumina HiSeq RNA sequencing
   platform_summary:
      NA
   platform_manufacturer:
      Illumina
   platform_distribution:
      sequencing
   platform_accession:
      NA
   platform_technology:
      RNA sequencing

Preprocessing: default
featureData(eset):
An object of class 'AnnotatedDataFrame'
  featureNames: ? A1BG ... ZZZ3 (20502 total)
  varLabels: probeset gene
  varMetadata: labelDescription

Details

assayData: 20502 features, 261 samples
Platform type: NA
Overall survival time-to-event summary (in years):
Call: survfit(formula = Surv(time, cens) ~ -1)

   5 observations deleted due to missingness
records   n.max n.start  events  median 0.95LCL 0.95UCL
 256.00  256.00  256.00  143.00    3.62    3.19    4.03

---------------------------
Available sample meta-data:
---------------------------

alt_sample_name:
   Length     Class      Mode
      261 character character

unique_patient_ID:
   Length     Class      Mode
      261 character character

sample_type:
tumor
  261

histological_type:
ser
261

primarysite:
other    ov
    1   260

summarygrade:
high  low NA's
 226   29    6

summarystage:
early  late  NA's
   18   242     1

tumorstage:
   2    3    4 NA's
  18  209   33    1

substage:
   b    c NA's
  16  211   34

grade:
   1    2    3    4 NA's
   1   28  225    1    6

age_at_initial_pathologic_diagnosis:
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.
  34.00   51.00   58.00   58.84   66.00   87.00

pltx:
   n    y NA's
  17  215   29

tax:
   n    y NA's
  17  215   29

neo:
   n NA's
 232   29

days_to_tumor_recurrence:
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's
    9.0   225.0   426.5   585.3   755.0  5480.0      19

recurrence_status:
norecurrence   recurrence
         123          138

days_to_death:
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's
    9.0   341.8   878.0  1018.0  1446.0  5480.0       5

vital_status:
deceased   living     NA's
     143      114        4

site_of_tumor_first_recurrence:
locoregional   metastasis         NA's
          82           56          123

primary_therapy_outcome_success:
  completeresponse    partialresponse progressivedisease      stabledisease
               147                 30                 15                 15
              NA's
                54

debulking:
   optimal suboptimal       NA's
       171         60         30

percent_normal_cells:
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's
  0.000   0.000   0.000   2.066   0.000  55.000       5

percent_stromal_cells:
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's
   0.00    5.00   10.00   11.43   15.00   70.00       4

percent_tumor_cells:
   Min. 1st Qu.  Median    Mean 3rd Qu.    Max.    NA's
   0.00   77.00   85.00   82.07   90.00  100.00       4

uncurated_author_metadata:
   Length     Class      Mode
      261 character character