An analysis of cancer-related alternative splicing through a genomics-based approach

Extract: In the past few years, many studies have suggested that alternative splicing is a widespread mechanism of functional regulation in the human genome. Cancer-associated splice variants have also been reported for genes such as EGFR, CD44, and recently many others. High throughput genomics data, such as those obtained from EST (expressed sequence tag) sequencing, have provided a major new opportunity for discovering cancer-specific alterations in splicing. Over 4 million human ESTs have been sequenced, and most can be classified both by their tissue of origin and whether they were derived from a tumor or normal tissue sample. Here, we summarize our work on 1) genome-wide detection of cancer-specific splicing, 2) independent validation, 3) functional impact, and 4) discovery of novel transcripts characteristic of normal tissues, followed by an example.