Comprehensive molecular pathology analysis of small bowel adenocarcinoma reveals novel targets with potential for clinical utility

Oncotarget
Muhammad A AlviManuel Salto-Tellez

Abstract

Small bowel accounts for only 0.5% of cancer cases in the US but incidence rates have been rising at 2.4% per year over the past decade. One-third of these are adenocarcinomas but little is known about their molecular pathology and no molecular markers are available for clinical use. Using a retrospective 28 patient matched normal-tumor cohort, next-generation sequencing, gene expression arrays and CpG methylation arrays were used for molecular profiling. Next-generation sequencing identified novel mutations in IDH1, CDH1, KIT, FGFR2, FLT3, NPM1, PTEN, MET, AKT1, RET, NOTCH1 and ERBB4. Array data revealed 17% of CpGs and 5% of RNA transcripts assayed to be differentially methylated and expressed respectively (p < 0.01). Merging gene expression and DNA methylation data revealed CHN2 as consistently hypermethylated and downregulated in this disease (Spearman -0.71, p < 0.001). Mutations in TP53 which were found in more than half of the cohort (15/28) and Kazald1 hypomethylation were both were indicative of poor survival (p = 0.03, HR = 3.2 and p = 0.01, HR = 4.9 respectively). By integrating high-throughput mutational, gene expression and DNA methylation data, this study reveals for the first time the distinct molecular profile o...Continue Reading

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Citations

Jul 25, 2017·Scandinavian Journal of Gastroenterology·Gustaw LechMaciej Słodkowski
Oct 26, 2018·The Oncologist·Suneel Deepak KamathAparna Kalyan
Sep 22, 2017·British Journal of Cancer·Muhammad A AlviManuel Salto-Tellez
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Mar 30, 2021·Frontiers in Oncology·Miguel Cordova-DelgadoMarcelo Garrido
May 21, 2021·PloS One·Akiyoshi TsuboiKazuaki Chayama
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Datasets Mentioned

BETA
PRJNA261313
GSE61465
GSE61467

Methods Mentioned

BETA
MDS
PCA
GTPase
surgical resection
chips
Assay
PCR

Software Mentioned

WGCNA
Ion OneTouch 2
PyroMark assay design
randomForest
NetBioV
Ion Torrent
kmeans
Finch TV
genefilter
RnBead

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