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Panel gene profiling of small bowel adenocarcinoma, results from the NADEGE prospective cohort

Abstract : Small bowel adenocarcinoma (SBA) is a rare tumour. Large genomic analyses with prognostic assessments are lacking. The NADEGE cohort has enrolled 347 patients with all stage SBA from 2009 to 2012. Next generation sequencing investigates the presence of 740 hotspot somatic mutations in a panel of 46 genes involved in carcinogenesis. The mismatch repair (MMR) status was assessed by immunochemistry. We have collected 196 tumour samples and 125 had conclusive results for mutation analysis. The number of mutations was 0 in 9.6% of tumours, only 1 in 32.0%, 2 in 26.4% and ≥ 3 in 32.0%. Altogether, at least one genomic alteration was observed in 90.4% of tumour. The most frequent genomic alteration was in KRAS (44.0%), TP53 (38.4%), PIK3CA (20.0%), APC (18.4%), SMAD4 (14.4%) and ERBB2 (7.2%) genes. KRAS mutations were more frequent in synchronous metastatic tumours than in localized tumours (72.7% vs 38.2%, P = 0.003). There was no significant difference in the mutation rates according to primary location for the most frequently altered gene. ATM, FGFR3 and FGFR1 gene alterations were associated with Lynch syndrome and IDH1 mutations with Crohn disease. dMMR tumours were associated with younger age, localized tumours, less KRAS but more SMARCB1 mutations. No genomic alteration was associated with overall survival. There is a trend for better survival in patient with dMMR tumours. In conclusion, there is a different genomic alteration profile in SBA according to predisposing diseases. No association between genomic alterations and prognoses was observed except for a trend of better prognoses associated with dMMR.
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https://hal.archives-ouvertes.fr/hal-03038573
Contributor : Laurent Jonchère <>
Submitted on : Tuesday, December 15, 2020 - 3:56:33 PM
Last modification on : Tuesday, September 7, 2021 - 3:44:38 PM
Long-term archiving on: : Tuesday, March 16, 2021 - 7:58:29 PM

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Thomas Aparicio, Magali Svrcek, Julie Henriques, Pauline Afchain, Astrid Lièvre, et al.. Panel gene profiling of small bowel adenocarcinoma, results from the NADEGE prospective cohort. International Journal of Cancer, Wiley, 2021, 148 (7), pp.1731-1742. ⟨10.1002/ijc.33392⟩. ⟨hal-03038573⟩

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