Título:	ERBB2 gene as a potential therapeutic target in small bowel adenocarcinoma
Autor(es):	Laforest, Anais Aparicio, Thomas Zaanan, Aziz Pittella-Silva, Fabio Didelot, Audrey Desbeaux, Aurélien Le Corre, Delphine Benhaim, Leonor Pallier, Karine Aust, Daniela Pistorius, Steffen Blons, Hélène Svrcek, Magali Laurent-Puig, Pierre
Assunto:	Genes Mutações Intestino delgado - câncer Sequenciamento genômico
Data de publicação:	Jul-2014
Editora:	Elsevier
Referência:	LAFLOREST, Anais et al. ERBB2 gene as a potential therapeutic target in small bowel adenocarcinoma. European Journal of Cancer, v. 50, n. 10, p. 1740-1746, jul. 2014. DOI: https://doi.org/10.1016/j.ejca.2014.04.007.
Abstract:	Aim of the study Small bowel adenocarcinoma (SBA) is a rare and aggressive tumour with poor outcomes. Because of its low incidence, the number prospective studies remains insufficient leading to poor knowledge and absence of standard of care. Aiming to better understand small bowel carcinogenesis we investigated the frequency of somatic mutations in a large data set of patients in more than 740 mutational hotspots among 46 genes. Methods In total, 83 SBA cases were selected from two European databases. The sequencing was performed using the Ion 316 Chip. Additionally we looked into ERBB2 expression and microsatellite instability (MSI) status. Results The tumours most frequently were duodenal (47%) and stage ⩾3 (63%). Eight genes were mutated with a frequency >5%: KRAS, TP53, APC, SMAD4, PIK3CA, ERBB2, BRAF and FBXW7. ERBB2 alterations are present in 10 patients (12%) through mutations (7 cases) or amplifications (3 cases). ERBB2 mutations were significantly associated with duodenal tumour location (P = 0.04). In this group, there was a positive association with dMMR status (P = 0.006) and APC mutation (P = 0.02) but negative association with p53 mutations (P = 0.038). Conclusions This study describes the first large screening of somatic mutations in SBA using next generation sequencing. The ERBB2 mutation was revealed to be one of the most frequent alterations in SBA with a distribution dependent on tumour location. In most cases ERBB2 mutation was identical (p.L755S). In clinical practice, this may suggest that more than 10% of the patients with SBA could be treated using an anti-ERBB2-targeted agent.
DOI:	https://doi.org/10.1016/j.ejca.2014.04.007
Versão da editora:	https://www.sciencedirect.com/science/article/pii/S0959804914005929?via%3Dihub#!
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