Genomic Alterations of NTRK, POLE, ERBB2, and Microsatellite Instability Status in Chinese Patients with Colorectal Cancer
| Autor: | Weifeng Wang, Xinyu Chen, Jian Wang, Yun Guo, Kai Wang, Samuel J. Klempner, Jiaochun Shi, Min Xiao, Shuang Wang, Xian-Ling Guo |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Oncology China Cancer Research medicine.medical_specialty Cancer Diagnostics and Molecular Pathology DNA Copy Number Variations Receptor ErbB-2 Colorectal cancer medicine.disease_cause Fusion gene 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans ERBB2 amplification Copy-number variation Receptor trkA Poly-ADP-Ribose Binding Proteins Indel neoplasms Gene business.industry Microsatellite instability DNA Polymerase II Genomics Middle Aged medicine.disease DNA polymerase ε Tumor mutational burden digestive system diseases 030104 developmental biology 030220 oncology & carcinogenesis Mutation Cohort Tropomyosin receptor kinase Female Microsatellite Instability KRAS Colorectal Neoplasms business |
| Zdroj: | The Oncologist |
| ISSN: | 1549-490X 1083-7159 |
| DOI: | 10.1634/theoncologist.2020-0356 |
| Popis: | Background The increasing molecular characterization of colorectal cancers (CRCs) has spurred the need to look beyond RAS, BRAF, and microsatellite instability (MSI). Genomic alterations, including ERBB2 amplifications and mutations, POLE mutations, MSI, and NTRK1–3 fusions, have emerged as targets for matched therapies. We sought to study a clinically annotated Chinese cohort of CRC subjected to genomic profiling to explore relative target frequencies. Methods Tumor and matched whole blood were collected from 609 Chinese patients with CRC. Extracted DNA was analyzed for all classes of genomic alterations across 450 cancer‐related genes, including single‐nucleotide variations (SNVs), short and long insertions and deletions (indels), copy number variations, and gene rearrangements. Next‐generation sequencing–based computational algorithms also determined tumor mutational burden and MSI status. Results Alterations in TP53 (76%), APC (72%), and KRAS (46%) were common in Chinese patients with CRC. For the first time, the prevalence of NTRK gene fusion was observed to be around 7% in the MSI‐high CRC cohort. Across the cohort, MSI was found in 9%, ERBB2 amplification in 3%, and POLE pathogenic mutation in 1.5% of patients. Such results mostly parallel frequencies observed in Western patients. However, POLE existed at a higher frequency and was associated with large tumor T‐cell infiltration. Conclusion Comparing to the Western counterparts, POLE mutations were increased in our cohort. The prevalence of NTRK gene fusion was around 7% in the MSI‐high CRC cohort. Increased adoption of molecular profiling in Asian patients is essential for the improvement of therapeutic outcomes. Implications for Practice The increasing use of genomic profiling assays in colorectal cancer (CRC) has allowed for the identification of a higher number of patient subsets benefiting from matched therapies. With an increase in the number of therapies, assays simultaneously evaluating all candidate biomarkers are critical. The results of this study provide an early support for the feasibility and utility of genomic profiling in Chinese patients with CRC. The emergence of precision medicine has identified genomic variants, such as NTRK gene fusion, microsatellite instability (MSI), HER2 amplification, and POLE pathogenic mutation, as potential agonistic biomarkers for immune or targeted therapies. This article examines NTRK, HER2, and POLE in a cohort of Chinese patients with colorectal cancer. |
| Databáze: | OpenAIRE |
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