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Published in: Journal of Cancer Research and Clinical Oncology 9/2023

21-01-2023 | Colorectal Cancer | Research

Driver and targetable alterations in Chinese patients with small bowel carcinoma

Authors: Jun Li, Xiaomo Li, Ningning Dong, Shu Yan, Chao Jing, Tonghui Ma, Wei Li, Chenghai Zhang, Yi Cai, Wei Deng

Published in: Journal of Cancer Research and Clinical Oncology | Issue 9/2023

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Abstract

Purpose

Small bowel carcinoma (SBA) is a rare gastrointestinal cancer with a poor prognosis. Recent genomic profiling studies revealed that the landscape of molecular alterations in SBA was distinct from colorectal cancer (CRC) and gastric cancer (GC). To explore driver and targetable alterations in SBA, we performed next-generation sequencing in 107 Chinese SBA patients.

Methods

DNA from paraffin-embedded SBA samples and the corresponding peripheral blood control samples were analyzed through a next-generation sequencing panel. Somatic alterations including point mutations, indels, copy number alterations, gene fusions as well as pathogenic germline variants were characterized.

Results

More than half of SBA cases carried KRAS mutations, including canonical (G12, G12, Q61) and atypical mutations (A146, L19, and K117). To our best knowledge, this was the first report of rare driver alterations including KRAS A146V/L19F, PIK3CA N345K/G364R/Q546E, and ZKSCAN1-MET fusion in SBA. Compared to KRAS-mutant patients, alternative activating alterations were enriched in KRAS wild-type patients, and some of them are targetable. Among BRAF-mutated SBA patients, class 1/2 BRAF mutants were mutually exclusive with RAS mutations, but class 3 BRAF mutants were not. Activating ERBB2 alternations, including amplification and activating mutations, represent the most common targetable alternation in this SBA cohort. Of note, the spectrums of BRAF and PIK3CA mutations in this Chinese SBA cohort were distinct from those of a European SBA cohort. Patients with three druggable mutations (PIK3CA, MAP2K1, KRAS G12C) had a high prevalence of concurring drivers, which may interfere with the clinical efficacy of single-target therapy.

Conclusion

Taken together, our work provided a comprehensive analysis of driver and targetable alterations in SBA, which can facilitate the practice of precision oncology in this challenging disease.
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Literature
go back to reference van der Klift HM, Jansen AM, van der Steenstraten N, Bik EC, Tops CM, Devilee P, Wijnen JT (2015) Splicing analysis for exonic and intronic mismatch repair gene variants associated with Lynch syndrome confirms high concordance between minigene assays and patient RNA analyses. Mol Genet Genom Med 3:327–345. https://doi.org/10.1002/mgg3.145CrossRef van der Klift HM, Jansen AM, van der Steenstraten N, Bik EC, Tops CM, Devilee P, Wijnen JT (2015) Splicing analysis for exonic and intronic mismatch repair gene variants associated with Lynch syndrome confirms high concordance between minigene assays and patient RNA analyses. Mol Genet Genom Med 3:327–345. https://​doi.​org/​10.​1002/​mgg3.​145CrossRef
Metadata
Title
Driver and targetable alterations in Chinese patients with small bowel carcinoma
Authors
Jun Li
Xiaomo Li
Ningning Dong
Shu Yan
Chao Jing
Tonghui Ma
Wei Li
Chenghai Zhang
Yi Cai
Wei Deng
Publication date
21-01-2023
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 9/2023
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-022-04521-0

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