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Cellular and Molecular Biology

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



Small bowel adenocarcinoma is a rare disease. The genomic profiling tumours according to clinical characteristics and its impact on the prognosis remains unclear.


A pooled analysis of clinical data, genomic profiling and MisMatch Repair (MMR) status from three databases was performed.


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).


There is a different genomic profile according to the stage and predisposing disease. dMMR and APC mutation in localized tumour predict a better prognosis.

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Fig. 1
Fig. 2: Overall survival according to APC mutation.
Fig. 3: Overall survival according to mismatch repair phenotype.

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Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.


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BIONADEGE and AGEO study were granted by INCa and sponsor by Assistance Publique Hôpitaux de Paris (Délégation à la Recherche Clinique). ARCAD-NADEGE cohort was granted by A.R.C.A.D. and sponsored by GERCOR.


BIONADEGE was supported by a grant from INCa (Programme Hospitalier de Recherche Translationelle Cancer, PRTK14 N°091) and a grant n° NA 2009 from the A.R.CA.D. foundation. AGEO study was supported by a grant from INCa (Programme Hospitalier de Recherche Clinique, PHRC AOM 09204).

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Authors and Affiliations



Study design: TA, MS, JH, DV and PLP. Data acquisition: TA, MS, AZ, SM, ACG, DT, JMG, DP, ET, GP, PA, CL, MP, TL, VB, FDF, SLD, SC, PLP. Statistical analysis: JH and DV. Manuscript preparation: TA, MS, JH, DV and PLP. Manuscript review: all authors.

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Correspondence to Thomas Aparicio.

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The authors declare no competing interests.

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This study was performed in accordance with the Declaration of Helsinki and was authorised by the ethics committee “Ile de France II” No. ID-RCB: 2008-A01058-47 for the French part and by the local Area Vasta Emilia Nord Ethics committee for the Italian part.

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Aparicio, T., Henriques, J., Svrcek, M. et al. Genomic profiling of small bowel adenocarcinoma: a pooled analysis from 3 databases. Br J Cancer 131, 49–62 (2024).

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