Panel gene profiling of small bowel adenocarcinoma: Results from the NADEGE prospective cohort

Thomas Aparicio (1) , Magali Svrcek (2, 3) , Julie Henriques (4) , Pauline Afchain (5) , Astrid Lièvre (6) , David Tougeron (7) , Johan Gagniere (8, 9) , Eric Terrebonne (10) , Guillaume Piessen (11, 12, 13) , Jean‐louis Legoux (14) , Cédric Lecaille (15) , Marc Pocard (16) , Jean‐marc Gornet (1) , Aziz Zaanan (17, 18, 19) , Sandrine Lavau-Denes (20) , Thierry Lecomte (21) , David Deutsch (22, 23) , Dewi Vernerey (2, 24, 4) , Pierre Laurent Puig (25, 18)

1 AP-HP - Hopital Saint-Louis [AP-HP]
2 GERCOR - Cooperator Multidisciplinary Oncology Group
3 CHU Saint-Antoine [AP-HP]
4 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
5 EPI-PHARE - EPI-PHARE
6 OSS - Oncogenesis, Stress, Signaling
7 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
8 CIC 1405 - Centre d'Investigation Clinique [CHU Clermont-Ferrand]
9 M2iSH - Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte
10 Hôpital Cardiologique du Haut Lévêque [Pessac]
11 Hôpital Claude Huriez [Lille]
12 GRECCAR - The French Research Group of Rectal Cancer Surgery = Groupe de Recherche en Chirurgie du Rectum
13 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
14 CHRO - Centre Hospitalier Régional d'Orléans
15 PBNA - Polyclinique Bordeaux Nord Aquitaine
16 CAP Paris-Tech (UMR_S_1275) - CArcinose Péritoine Paris-Technologies (ex-CART)
17 UPCité - Université Paris Cité
18 HEGP - Hôpital Européen Georges Pompidou [APHP]
19 Cancer Research and Personalized Medicine - CARPEM [Paris]
20 CHU Limoges
21 Hôpital Trousseau
22 Service de Gastro-entérologie [Avicenne]
23 Hôpital Avicenne [AP-HP]
24 Service d'Oncologie Médicale [CHRU Besançon]
25 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers

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%. Overall, 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 localised tumours (72.7% vs 38.2%, P = .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, localised 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.

Domaines: Cancer

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, 2021, 148 (7), pp.1731-1742. ⟨10.1002/ijc.33392⟩. ⟨hal-03038573v1⟩