PURPOSE: @entity4056 ( @entity4056 ) are the commonest malignancy of the small intestine; however, underlying pathogenic mechanisms remain poorly characterized. Whole-genome and -exome sequencing has demonstrated that SINETs are mutationally quiet, with the most frequent known mutation in the cyclin-dependent kinase inhibitor 1B gene ( @entity13525 ) occurring in only    8% of @entity5 , suggesting that alternative mechanisms may drive tumorigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling. This study represents the largest unbiased integrated genomic, epigenomic, and transcriptomic analysis undertaken in this @entity5 type. EXPERIMENTAL DESIGN: Here, we present data from integrated molecular analysis of SINETs (n = 97), including whole-exome or targeted @entity13525 sequencing (n = 29), HumanMethylation450 BeadChip (Illumina) array profiling (n = 69), methylated DNA immunoprecipitation sequencing (n = 16), copy-number variance analysis (n = 47), and Whole-Genome DASL (Illumina) expression array profiling (n = 43). RESULTS: Based on molecular profiling, SINETs can be classified into three groups, which demonstrate significantly different progression-free survival after resection of @entity5 (not reached at 10 years vs. 56 months vs. 21 months, P = 0.04). Epimutations were found at a recurrence rate of up to 85%, and 21 epigenetically dysregulated genes were identified, including @entity30411 (86%), @entity69781 (84%), @entity24154 (84%), and @entity35679 (74%). CONCLUSIONS: This is the first comprehensive integrated molecular analysis of SINETs. We have demonstrated that these @entity5 are highly epigenetically dysregulated. Furthermore, we have identified novel molecular subtypes with significant impact on progression-free survival. Clin Cancer Res; 1-9.   2015 AACR.

Prognostic Impact of Novel Molecular Subtypes of XXXX .

@entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'primary tumor', 'tumors'] @entity24154 :: ('2203', 'Gene') :: ['FBP1'] @entity4056 :: ('MESH:D007414', 'Disease') :: ['Small intestinal neuroendocrine tumors', 'SINET'] @entity35679 :: ('2696', 'Gene') :: ['GIPR'] @entity13525 :: ('1027', 'Gene') :: ['CDKN1B'] @entity30411 :: ('1044', 'Gene') :: ['CDX1'] @entity69781 :: ('1951', 'Gene') :: ['CELSR3']
@entity4056 :: (MESH:D007414,Disease) :: ['Small Intestinal Neuroendocrine Tumor']
