| Title | Driver and targetable alterations in Chinese patients with small bowel carcinoma |
| Authors | Li, Jun Li, Xiaomo Dong, Ningning Yan, Shu Jing, Chao Ma, Tonghui Li, Wei Zhang, Chenghai Cai, Yi Deng, Wei |
| Affiliation | Capital Med Univ, Beijing Friendship Hosp, Natl Clin Res Ctr Digest Dis, Beijing Digest Dis Ctr,Dept Gen Surg, Beijing, Peoples R China Hangzhou Jichenjunchuang Med Lab Co Ltd, Hangzhou, Peoples R China Capital Med Univ, Beijing Friendship Hosp, Natl Clin Res Ctr Digest Dis, Beijing Digest Dis Ctr,Dept Gastroenterol,Beijing, Beijing, Peoples R China Beijing Aerosp Gen Hosp, Dept Anorectal Surg, Beijing, Peoples R China Peking Univ, Canc Hosp & Inst, Dept Gastrointestinal Surg 4, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing, Peoples R China |
| Keywords | LYNCH SYNDROME COLON-CANCER INHIBITION DIFFERENTIATION MUTATIONS VARIANTS GENOMICS SOX9 MDM2 |
| Issue Date | Jan-2023 |
| Publisher | JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY |
| Abstract | PurposeSmall 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.MethodsDNA 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.ResultsMore 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.ConclusionTaken 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. |
| URI | http://hdl.handle.net/20.500.11897/669476 |
| ISSN | 0171-5216 |
| DOI | 10.1007/s00432-022-04521-0 |
| Indexed | SCI(E) |
| Appears in Collections: | 北京肿瘤医院 |
