Journal Article

Genomic profiling of small bowel adenocarcinoma: a pooled analysis from 3 databases

Terrebonne, Eric, Cascinu, Stefano, Manfredi, Sylvain, Lecomte, Thierry, Svrcek, Magali, Afchain, Pauline, Jary, Marine, Laurent Puig, Pierre, Zaanan, Aziz, Di Fiore, Frédéric, Henriques, Julie, Le Brun Ly, Valérie, Gornet, Jean-Marc, Lecaille, Cédric, Aparicio, Thomas, Pocard, Marc, Vernerey, Dewi, Piessen, Guillaume, Tougeron, David, Casadei-Gardini, Andrea, Rimini, Margherita

2024

Overview

Background Small bowel adenocarcinoma is a rare disease. The genomic profiling tumours according to clinical characteristics and its impact on the prognosis remains unclear. Methods A pooled analysis of clinical data, genomic profiling and MisMatch Repair (MMR) status from three databases was performed. Results A total of 188 tumour samples were analysed. A predisposing disease was reported in 22.3%, mainly Lynch syndrome and Crohn’s disease. The tumours were localized in 80.2% and metastatic in 18.8%. The most frequent mutations were KRAS (42.0%) among them 7/79 are G12C , TP53 (40.4%), APC (19.1%), PIK3CA (18.6%), SMAD4 (12.8%) and ERBB2 (9.6%). Mutation distribution differed according to predisposing disease for TP53 , ERBB2, IDH1, FGFR3, FGFR1 and KDR. KRAS and SMAD4 mutations were more frequent in metastatic tumour, whereas ERBB2 mutations were absent in metastatic tumour. For localized tumour, APC mutation was independently associated with a poor overall survival (OS) ( p  = 0.0254). 31.8% of localized tumours and 11.3% of metastatic tumours were dMMR (29.8% of the entire cohort). A dMMR status was associated with a better OS (HR = 0.61 [0.39–0.96], p  = 0.0316). Conclusions There is a different genomic profile according to the stage and predisposing disease. dMMR and APC mutation in localized tumour predict a better prognosis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/67/1504 / 692/4028/67/69 / Adenocarcinoma / Adenocarcinoma - genetics / Adenocarcinoma - pathology / Adenomatous polyposis coli / Adult / Aged / Aged, 80 and over / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Colorectal cancer / Crohn's disease / DNA Mismatch Repair - genetics / Drug Resistance / Epidemiology / ErbB-2 protein / Female / Fibroblast growth factor receptor 1 / Fibroblast growth factor receptors / Gene Expression Profiling / Genetic disorders / Genomic analysis / Humans / Intestinal Neoplasms - genetics / Intestinal Neoplasms - mortality / Intestinal Neoplasms - pathology / Intestine / Intestine, Small - pathology / Male / Medical prognosis / Metastases / Metastasis / Middle Aged / Mismatch repair / Molecular Medicine / Mutation / Oncology / Prognosis / Smad4 protein / Small intestine / Tumors