1424P - Genetic alterations in GISTs using whole exome and transcriptome sequencing

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics GIST
Pathology/Molecular Biology
Personalised/Precision Medicine
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Presenter Mineui Hong
Citation Annals of Oncology (2014) 25 (suppl_4): iv494-iv510. 10.1093/annonc/mdu354
Authors M. Hong1, G. Kang2, K. Kim1
  • 1Pathology, Samsung Medical Center, 135710 - Seoul/KR
  • 2Pathology, Inje University Sanggye Paik Hospital, seoul/KR



To explore genomic alterations underlying gastrointestinal stromal tumors (GISTs), we integrated the whole genome sequencing (WGS), whole exome sequencing and transcriptome sequencing results from 9 GISTs.


Exonic regions of the 9 tumors contained 306 somatic variants (mean: 34; range: 20-54) corresponding to a mean of 0.66 mutations per megabase including 172 missense, 13 nonsense, 3 stop codon loss, 16 splice-site, 11 small insertion and deletions (indels) and 90 synonymous mutations.


From the WGS data set, a total of 4,743 gene rearrangements were detected in two wild-type GISTs. However, when the fusions were validated by RNA-seq reads, no rearrangement predicted to produce an aberrant fusion transcript. One of the most frequently involved genes was IGF2, which fused to a number of different partners. Some of the partner genes (such as EPS15, CCND1, FUS, HNRNPA2B1 and LASP1) have been observed in oncogenic fusions in other cancers (mostly in leukemia), according to the Cancer Gene Census. We also identified three highly recurrent, read-through gene fusions, including POLA2-CDC42EP2 (n=7), C8orf42-FBXO25 (n=4) and STX16-NPEPL1 (n=3). KEGG pathway analysis of the overexpressed gene lists revealed significant differences in the level of pathway activation between tumor subtypes; GISTs in the small intestine showed activation of the Jak-STAT pathway while gastric wild-type GISTs showed activated MAPK signaling pathway. We also identified a total of 400 outlier genes with copy number gain across 9 tumor samples and AMACR, a diagnostic marker and therapeutic target for prostate cancer was recurrent in 2 GISTs.


In conclusion, we identified frequent genetic alterations and tumor-specific activated signaling pathways in GISTs and will facilitate further investigation to develop new therapeutic options for GIST patients.


All authors have declared no conflicts of interest.