Universität zu Köln

Quaas, Alexander, Heydt, Carina, Waldschmidt, Dirk, Alakus, Hakan, Zander, Thomas, Goeser, Tobias, Kasper, Philipp, Bruns, Christiane, Brunn, Anna, Roth, Wilfried, Hartmann, Nils, Bunck, Anne, Schmidt, Matthias, Buettner, Reinhard and Merkelbach-Bruse, Sabine (2019). Alterations in ERBB2 and BRCA and microsatellite instability as new personalized treatment options in small bowel carcinoma. BMC Gastroenterol., 19. LONDON: BMC. ISSN 1471-230X

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Abstract

BackgroundCarcinomas of the small bowel are rare tumors usually with dismal prognosis. Most recently, some potentially treatable molecular alterations were described. We emphasize the growing evidence of individualized treatment options in small bowel carcinoma.MethodsWe performed a DNA- based multi-gene panel using ultra-deep sequencing analysis (including 14 genes with up to 452 amplicons in total; KRAS, NRAS, HRAS, BRAF, DDR2, ERBB2, KEAP1, NFE2L2, PIK3CA, PTEN, RHOA, BRCA1, BRCA2 and TP53) as well as an RNA-based gene fusion panel including ALK, BRAF, FGFR1, FGFR2, FGFR3, MET, NRG1, NTRK1, NTRK2, NTRK3, RET and ROS1 on eleven formalin fixed and paraffin embedded small bowel carcinomas. Additionally, mismatch-repair-deficiency was analyzed by checking the microsatellite status using the five different mononucleotide markers BAT25, BAT26, NR-21, NR-22 and NR-27 and loss of mismatch repair proteins using four different markers (MLH1, MSH6, MSH2, PMS2).ResultsIn five out of eleven small bowel carcinomas we found potentially treatable genetic alterations. Three patients demonstrated pathogenic (class 5) BRCA1 or BRCA2 mutations - one germline-related in a mixed neuroendocrine-non neuroendocrine neoplasm (MiNEN). Two additional patients revealed an activating ERBB2 mutation or PIK3CA mutation.Furthermore two tumors were highly microsatellite-instable (MSI-high), in one case associated to Lynch-syndrome. We did not find any gene fusions.ConclusionOur results underscore, in particular, the relevance of potentially treatable molecular alterations (like ERBB2, BRCA and MSI) in small bowel carcinomas. Further studies are needed to proof the efficacy of these targeted therapies in small bowel carcinomas.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Heydt, Carina UNSPECIFIED UNSPECIFIED UNSPECIFIED Waldschmidt, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Goeser, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Kasper, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED Brunn, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Roth, Wilfried UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Nils UNSPECIFIED UNSPECIFIED UNSPECIFIED Bunck, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-156973
DOI:	10.1186/s12876-019-0942-z
Journal or Publication Title:	BMC Gastroenterol.
Volume:	19
Date:	2019
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1471-230X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RIBOSE POLYMERASE INHIBITORS; SOMATIC MUTATIONS; OVARIAN; CANCER; ADENOCARCINOMA; SURVIVAL; BLOCKADE; TARGET Multiple languages Gastroenterology & Hepatology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15697