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

Br J Cancer. 2024 Jul;131(1):49-62. doi: 10.1038/s41416-024-02687-7. Epub 2024 May 14.


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.

MeSH terms

  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Mismatch Repair / genetics
  • Female
  • Gene Expression Profiling
  • Humans
  • Intestinal Neoplasms* / genetics
  • Intestinal Neoplasms* / mortality
  • Intestinal Neoplasms* / pathology
  • Intestine, Small / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Prognosis