Abstract 1823P
Background
Duodenal carcinomas (DC) are malignancies from the small bowel that can overlap pancreatobiliary (PBC) and colon cancer (CC) in histologic and molecular features. In this study, we assessed the somatic mutational landscapes of a combined cohort of DC, PBC, and CC from 19 institutions participating in the GENIE Consortium Cohort (v9.0) and examined the differential mutational landscape of DC as compared with PBC and CC, along with the clinical actionability of unique mutations identified in DC.
Methods
We assessed the 9th data release of the GENIE Consortium Cohort encompassing targeted sequencing data from 125 DC, 3,886 PCB and 6,386 CC. All patient samples were de-identified and encoded with GENIE sample codes. Clinical features and somatic mutations including single-nucleotide variants, small indels, fusions, and copy number alterations (CNAs) were retrieved from cBioPortal and SAGE Bionetworks. Gene enrichment analyses and actionability was examined using the OncoKB publicly available knowledgebase.
Results
Median age at which sequencing was reported: 59, 62, and 65 for CC, DC, and PCB, respectively (p<0.005). We observed no difference in the median number of genomic alterations per tested sample between DC and CC (8 and 7, respectively; p=NS). Comparatively, PBC presented a median number of 4 mutations per tested sample (p<0.005). After gene enrichment analyses, we found only 4 out of 1,176 genes differentially mutated in DC as compared to CC (ERBB2, CDKN2A, ERBB3, MAP2K1). On the other hand, comparison between DC and PBC showed that 63 out of 1,064 genes were differentially mutated in DC, preeminently those related to the WNT/ß-catenin and NOTCH pathways (APC, AXIN1, CTNNB1, NOTCH1).
Conclusions
Real-world data from over 10,000 tumor samples in the Genie Cohort Consortium support that the genomic mutational landscape of DC is closer to CC than to PBC. Further analyses of gene actionability will be presented in the meeting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Dr. Alessandro Leal.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.