1. Alternative promoters in gastric cancer (GC).
Alternative promoters in gastric cancer (GC). A, UCSC browser track of the HNF4A gene. Gastric cancer and matched gastric normal samples have equal H3K4me3 signals at the canonical HNF4A promoter. However, an alternative promoter, seen by H3K4me3 gain, can be observed at a downstream TSS in gastric cancers compared with matched normals. At the RNA level, both in-house and TCGA STAD samples also show gain of gene expression at the alternate promoter TSS compared with normal samples. B, UCSC browser track of the EPCAM gene. Another example of alternative promoter usage at a downstream TSS. Gain of H3K4me3 is observed at a TSS downstream of the canonical promoter, while the canonical promoter exhibits equal H3K4me3 signals in gastric cancer and gastric normal. Gain of RNA-seq expression can also be observed in gastric cancer at the alternative promoter–driven transcript in both in-house and TCGA STAD samples. C, UCSC browser track of the RASA3 gene, demonstrating H3K4me3 and RNA-seq signals highlighting gain of promoter activity at an unannotated TSS (dark gray box) corresponding to a novel N-terminal truncated RASA3 transcript. Expression of this variant transcript was validated through 5′ Rapid Amplification of cDNA Ends (RACE) in gastric cancer lines (bottom). D, Functional domains of the translated RASA3 canonical and alternate isoform. The alternate transcript is predicted to encode a RASA3 protein missing the RASGAP domain. E, Effect of overexpression of RASA3 canonical (CanT) and alternate (SomT) isoforms on the migration capability of SNU1967 (top) and GES1 (bottom) cells. Representative images of RASA3-Ctl (empty vector), RASA3-CanT, and RASA3-SomT in migration assays (n = 3). Bar plots show the percentage area of migrated cells versus the area of Transwell membrane. Data are shown as mean ± SD; n = 3 (**, P < 0.01; Student one sided t test).
Aditi Qamra et al. Cancer Discov 2017;7:
©2017 by American Association for Cancer Research