An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

SSX cancer testis antigens are expressed in most multiple myeloma patients: co-expression of SSX1, 2, 4, and 5 correlates with adverse prognosis and high frequencies of SSX-positive PCs.

Contains fulltext : 48545.pdf (publisher's version ) (Closed access)Cancer testis antigens (CTAs) are tumor-specific antigens that may be useful targets for cancer vaccines. Here, CTA expression was examined in multiple myeloma (MM), a B-cell cancer characterized by malignant plasma cells (PCs) in the bone marrow (BM), and monoclonal gammopathy of undetermined significance (MGUS), a condition that can progress to MM. We screened a panel of patient BMs at different stages of malignancy for CTA expression by reverse transcription polymerase chain reaction RT-PCR. Here, SSX (synovial sarcoma, X chromosome) emerged as a promising candidate for an MM vaccine, having a profile similar to currently studied CTA, NY-ESO-1, and MAGE. SSX1, 2, 4, and 5 expression was studied further in 114 MM (total SSX, 61% of patients; SSX1, 42%; SSX2, 23%; SSX4, 38%; SSX5, 35%), 45 MGUS (total SSX, 24% of patients; SSX1, 9%; SSX4, 20%), and 12 control (0/12, 0%) subjects. Several expression patterns were observed, the most predominant being co-expression of SSX1, 2, 4, and 5 (called group A expression, in 20% of MM), which correlated with reduced survival (P=0.0006). Of the four genes, SSX2 had the strongest association with reduced survival (P=0.0001). SSX protein expression ranged from 13.5% of PCs in an SSX1/SSX4 co-expressor to as high as 88% of PCs in group A expressor, exceeding reported frequencies of NY-ESO-1 and MAGE in MM. In single PCs from group A patients, we detected variable degrees of SSX co-expression, emphasizing the heterogeneity of CTA expression within tumor cell populations. These results demonstrate that SSX is a frequently expressed CTA in MM and highlight its potential as an MM vaccine candidate