Academic Journal
NTRK oncogenic fusions are exclusively associated with the serrated neoplasia pathway in the colorectum and begin to occur in sessile serrated lesions
| العنوان: | NTRK oncogenic fusions are exclusively associated with the serrated neoplasia pathway in the colorectum and begin to occur in sessile serrated lesions |
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| المؤلفون: | Kim, Jung Ho, Hong, Jeong Hoon, Choi, Yoon-La, Lee, Ji Ae, Seo, Mi-kyoung, Lee, Mi-Sook, An, Sung Bin, Sung, Min Jung, Cho, Nam-Yun, Kim, Sung-Su, Shin, Young Kee, Kim, Sangwoo, Kang, Gyeong Hoon |
| المساهمون: | Shin, Young Kee, Kang, Gyeong Hoon |
| بيانات النشر: | John Wiley & Sons Inc. |
| سنة النشر: | 2021 |
| المجموعة: | Seoul National University: S-Space |
| الوصف: | Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are emerging tissue-agnostic drug targets in malignancies including colorectal carcinomas (CRCs), but their detailed landscape in the context of various colorectal carcinogenesis pathways remains to be investigated. In this study, pan-tropomyosin receptor kinase (TRK) protein expression was assessed by immunohistochemistry (IHC) in retrospectively collected colorectal epithelial tumor tissues, including 441 CRCs [133 microsatellite instability-high (MSI-high) and 308 microsatellite stable (MSS)] and 595 premalignant colorectal lesions (330 serrated lesions and 265 conventional adenomas). TRK-positive cases were then subjected to next-generation sequencing and/or fluorescence in situ hybridization to confirm NTRK rearrangements. TRK IHC positivity was not observed in any of the MSS CRCs, conventional adenomas, traditional serrated adenomas, or hyperplastic polyps, whereas TRK positivity was observed in 11 of 58 (19%) MLH1-methylated MSI-high CRCs, 4 of 23 (17%) sessile serrated lesions with dysplasia (SSLDs), and 5 of 132 (4%) sessile serrated lesions (SSLs). The 11 TRK-positive MSI-high CRCs commonly harbored CpG island methylator phenotype-high (CIMP-high), MLH1 methylation, BRAF/KRAS wild-type, and NTRK1 or NTRK3 fusion (TPM3-NTRK1, TPR-NTRK1, LMNA-NTRK1, SFPQ-NTRK1, ETV6-NTRK3, or EML4-NTRK3). Both NTRK1 or NTRK3 rearrangement and BRAF/KRAS wild-type were detected in all nine TRK-positive SSL(D)s, seven of which demonstrated MSS and/or CIMP-low. TRK expression was selectively observed in distorted serrated crypts within SSLs and was occasionally localized at the base of serrated crypts. NTRK fusions were detected only in SSLs of patients aged >= 50 years, whereas BRAF mutation was found in younger age-onset SSLs. In conclusion, NTRK-rearranged colorectal tumors develop exclusively through the serrated neoplasia pathway and can be initiated from non-dysplastic SSLs without BRAF/KRAS mutations prior to full occurrence of MSI-high/CIMP-high. (c) ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| ردمك: | 978-0-00-698363-7 0-00-698363-4 |
| تدمد: | 0022-3417 |
| Relation: | Journal of Pathology, Vol.255 No.4, pp.399-411; https://hdl.handle.net/10371/179806; 000698363400001; 2-s2.0-85115345911; 149249 |
| الاتاحة: | https://hdl.handle.net/10371/179806 |
| رقم الانضمام: | edsbas.61D1EFE2 |
| قاعدة البيانات: | BASE |
| ردمك: | 9780006983637 0006983634 |
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| تدمد: | 00223417 |