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Cellular and Molecular Biology

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

British Journal of Cancer (2024)Cite this article

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Abstract

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.

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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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Acknowledgements

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.

Funding

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).

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Digestive Oncology, Saint Louis Hospital, APHP, Université de Paris Cité, Paris, France

    Thomas Aparicio & Jean-Marc Gornet

  2. Methodology and Quality of Life Unit in Oncology, CHU Besançon, Hôpital Jean Minjoz, Besançon, France

    Julie Henriques & Dewi Vernerey

  3. Bourgogne Franche-Comté University, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France

    Julie Henriques & Dewi Vernerey

  4. Sorbonne Université, Department of Pathology, Saint Antoine Hospital, APHP, Paris, France

    Magali Svrcek

  5. Department of Gastroenterology and Digestive Oncology, Georges Pompidou Hospital, APHP, Université de Paris Cité, Paris, France

    Aziz Zaanan

  6. Digestive Cancer Registry of Burgundy, INSERM, LNC UMR1231, University Bourgogne Franche-Comté, Dijon-Bourgogne University Hospital, Dijon, France

    Sylvain Manfredi

  7. Department of Oncology, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy

    Andrea Casadei-Gardini, Margherita Rimini & Stefano Cascinu

  8. Department of Hepato-Gastroenterology, CHU de Poitiers, Poitiers, France

    David Tougeron

  9. Department of Digestive and Hepatobiliary Surgery, University Hospital of Clermont-Ferrand, U1071 INSERM, Clermont-Auvergne University, Clermont-Ferrand, France

    Marine Jary

  10. Department of Gastroenterology, CHU Haut-Lévêque, Pessac, France

    Eric Terrebonne

  11. Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, University Lille, Lille, France

    Guillaume Piessen

  12. Department of Oncology, Saint Antoine Hospital, APHP, Paris, France

    Pauline Afchain

  13. Department of Gastroenterology, Polyclinic Bordeaux Nord, Bordeaux, France

    Cédric Lecaille

  14. Department of Digestive Surgery, Pitié-Salpétrière Hospital, APHP, Paris, France

    Marc Pocard

  15. Department of Hepato-Gastroenterology and Digestive Oncology, Trousseau Hospital, CHU Tours, Tours, France

    Thierry Lecomte

  16. Department of Digestive Oncology, CHU Charles Nicolle, Rouen, France

    Frédéric Di Fiore

  17. Department of Oncology, CHU Dupuytren, Limoges, France

    Valérie Le Brun Ly

  18. Department of Biology, Georges Pompidou Hospital, APHP, Université de Paris Cité, Paris, France

    Pierre Laurent Puig

Authors
  1. Thomas Aparicio
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Contributions

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.

Corresponding author

Correspondence to Thomas Aparicio.

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The authors declare no competing interests.

Ethical approval

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 (2024). https://doi.org/10.1038/s41416-024-02687-7

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