Tumor-agnostic genomic and clinical analysis of BRAF fusions identifies actionable targets Journal Article
| Authors: | Chen, M. F.; Yang, S. R.; Tao, J. J.; Desilets, A.; Diamond, E. L.; Wilhelm, C.; Rosen, E.; Gong, Y.; Mullaney, K.; Torrisi, J.; Young, R. J.; Somwar, R.; Yu, H. A.; Kris, M. G.; Riely, G. J.; Arcila, M. E.; Ladanyi, M.; Donoghue, M. T. A.; Rosen, N.; Yaeger, R.; Drilon, A.; Murciano-Goroff, Y. R.; Offin, M. |
| Article Title: | Tumor-agnostic genomic and clinical analysis of BRAF fusions identifies actionable targets |
| Abstract: | Purpose: Even though BRAF fusions are increasingly detected directed therapies, of which 20 were evaluable for RECIST. Best in standard multigene next-generation sequencing panels, few response was partial response (N 1⁄4 2), stable disease (N 1⁄4 11), and reports have explored their structure and impact on clinical progressive disease (N 1⁄4 7). The median time on therapy was course. 1 month with MEK plus BRAF inhibitors [(N 1⁄4 11), range 0–18 Experimental Design: We collected data from patients with months] and 8 months for MEK inhibitors [(N 1⁄4 14), range 1–26 BRAF fusion–positive cancers identified through a genotyping months]. Nine patients remained on treatment for longer than protocol of 97,024 samples. Fusions were characterized and 6 months [pilocytic astrocytomas (N 1⁄4 6), Erdheim–Chester dis-reviewed for oncogenic potential (in-frame status, non-BRAF ease (N 1⁄4 1), extraventricular neurocytoma (N 1⁄4 1), and melapartner gene, and intact BRAF kinase domain). noma (N 1⁄4 1)]. Fifteen patients had acquired BRAF fusions. Results: We found 241 BRAF fusion–positive tumors from 212 Conclusions: BRAF fusions are found across histologies and patients with 82 unique 50 fusion partners spanning 52 histologies. represent an emerging actionable target. BRAF fusions have a diThirty-nine fusion partners were not previously reported, and 61 verse set of fusion partners. Durable responses to MAPK therapies were identified once. BRAF fusion incidence was enriched in were seen, particularly in pilocytic astrocytomas. Acquired BRAF pilocytic astrocytomas, gangliogliomas, low-grade neuroepithelial fusions were identified after targeted therapy, underscoring the tumors, and acinar cell carcinoma of the pancreas. Twenty-four importance of postprogression biopsies to optimize treatment at patients spanning multiple histologies were treated with MAPK- relapse in these patients. ©2024 American Association for Cancer Research. |
| Keywords: | adolescent; adult; child; human tissue; preschool child; aged; child, preschool; middle aged; young adult; major clinical study; sequence analysis; genetics; clinical trial; erlotinib; glioma; neoplasm; neoplasms; colorectal cancer; protein kinase inhibitor; pathology; bladder cancer; tumor marker; histology; protein kinase inhibitors; lung adenocarcinoma; oncogene proteins, fusion; genomics; neuroepithelioma; thyroid cancer; toxicity; acinar cell carcinoma; astrocytoma; b raf kinase; disease exacerbation; proto-oncogene proteins b-raf; braf protein, human; stomach tumor; molecularly targeted therapy; genotyping; molecular targeted therapy; pilocytic astrocytoma; selumetinib; procedures; mitogen activated protein kinase kinase inhibitor; response evaluation criteria in solid tumors; trametinib; high throughput sequencing; afatinib; mapk signaling; high-throughput nucleotide sequencing; very elderly; humans; human; male; female; article; cobimetinib; osimertinib; liquid biopsy; biomarkers, tumor; oncogenomics; oncogene fusion protein; tumor agnostic genomic |
| Journal Title: | Clinical Cancer Research |
| Volume: | 30 |
| Issue: | 17 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2024-09-01 |
| Start Page: | 3812 |
| End Page: | 3823 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-23-3981 |
| PUBMED: | 38922339 |
| PROVIDER: | scopus |
| PMCID: | PMC11371517 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding authors are Yonina Murciano-Goroff and Michael Offin -- Source: Scopus |
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