The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags

Abstract

Whereas genome sequencing defines the genetic potential of an organism, transcript sequencing defines the utilization of this potential and links the genome with most areas of biology. To exploit the information within the human genome in the fight against cancer, we have deposited some two million expressed sequence tags (ESTs) from human tumors and their corresponding normal tissues in the public databases. The data currently define Ϸ23,500 genes, of which only Ϸ1,250 are still represented only by ESTs. Examination of the EST coverage of known cancer-related (CR) genes reveals that <1% do not have corresponding ESTs, indicating that the representation of genes associated with commonly studied tumors is high. The careful recording of the origin of all ESTs we have produced has enabled detailed definition of where the genes they represent are expressed in the human body. More than 100,000 ESTs are available for seven tissues, indicating a surprising variability of gene usage that has led to the discovery of a significant number of genes with restricted expression, and that may thus be therapeutically useful. The ESTs also reveal novel nonsynonymous germline variants (although the one-pass nature of the data necessitates careful validation) and many alternatively spliced transcripts. Although widely exploited by the scientific community, vindicating our totally open source policy, the EST data generated still provide extensive information that remains to be systematically explored, and that may further facilitate progress toward both the understanding and treatment of human cancers.

Genetic services and testing in Brazil

“…These efforts resulted in the sequencing of the genome of Xylella fastidiosa in 2000 (Simpson et al 2000) and established an expert network on advanced projects in genomics, with international impact, whose most important product in human genetics was the Human Cancer Genome Project (2011). In this bold project, about 2 million DNA sequences of normal and tumor tissue were deposited in GENBANK (Brentani et al 2003) …”

Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer

“…Therefore, we constructed a cDNA microarray that is enriched with a collection of partial transcripts that map to intronic segments of known genes. We used a bioinformatics approach to select these from nearly one million ESTs that were generated by the Human Cancer Genome Project with the ORESTES technique (DiasNeto et al, 2000) from 24 distinct types of cancer and normal adjacent tissues, having sampled over 60% of the human genes (Camargo et al, 2001;Brentani et al, 2003). The resulting intron array was used to measure the expression profile of 27 prostate tumor samples with different degrees of differentiation (Gleason score, GS 5 to 10).…”

Pattern-Based Gene-Set Recognition for Interpreting Genome-Wide Gene Expression Profiles.

“…Two gene sets showing monotonous p-value dynamics were observed. Both were cancer-related gene sets (Brentani_Death, Brentani_Transcription_Factors) that were manually curated using expressed sequence tags [50]. The cancer-related transcription factors (Brentani_Transcription_Factors) displayed high significant p-values at 0h, and the p-values continuously increase along the 24 hour course.…”