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Mutually exclusive recurrent KRAS and MAP2K1 mutations in Rosai–Dorfman disease
| Content Provider | Scilit |
|---|---|
| Author | Garces, Sofia Medeiros, L. Jeffrey Patel, Keyur P. Li, Shaoying Pina-Oviedo, Sergio Li, Jingyi Garces, Juan C. Khoury, Joseph D. Yin, C. Cameron |
| Copyright Year | 2017 |
| Description | Journal: Modern Pathology Rosai–Dorfman disease is a histiocytic disorder with a poorly defined pathogenesis. Recent molecular studies have revealed recurrent mutations involving genes in the MAPK/ERK pathway in Langerhans cell histiocytosis and Erdheim–Chester disease. However, cases of Rosai–Dorfman disease have rarely been assessed. We performed next-generation sequencing to assess 134 genes on 21 cases of Rosai–Dorfman disease, including 13 women and 8 men with a median age of 43 years (range, 3–82). In all, 13 had extranodal, 5 had nodal, and 3 had coexistent nodal and extranodal disease. The head and neck region was the most common area involved (n=7). Mutation analysis detected point mutations in 7 (33%) cases, including KRAS (n=4) and MAP2K1 (n=3). No mutations were identified in ARAF, BRAF, PIK3CA, or any other genes assessed. Immunohistochemistry demonstrated p-ERK overexpression in 3 cases, all harboring MAP2K1 mutations. Patients carrying mutated genes were younger (median age, 10 vs 53 years, P=0.0347) with more pediatric patients (4/7 vs 1/14, P=0.0251). The presence of mutations correlated with location being more common in the head and neck region; 6/7 (86%) mutated vs 1/14 (7%) unmutated cases (P=0.0009). All 5 (100%) mutated cases with available staging information had a multifocal presentation, whereas only 3/11 (27%) unmutated patients had multifocal disease (P=0.0256). Treatment information was available in 10 patients, including radical resection (n=4), resection and radiation (n=3), and cladribine-based chemotherapy (n=3). With a median follow-up of 84 months (range, 7–352), 7 remained in clinical remission and 3 had persistent disease. No correlation between mutation status and clinical outcome was noted. In summary, we detected mutually exclusive KRAS and MAP2K1 mutations in one-third of cases of Rosai–Dorfman disease suggesting this subgroup are clonal and involve activation of MAPK/ERK pathway. Our data contribute to the understanding of the biology of Rosai–Dorfman disease and point to potential diagnostic and therapeutic targets. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837474/pdf https://www.nature.com/articles/modpathol201755.pdf |
| Ending Page | 1377 |
| Page Count | 11 |
| Starting Page | 1367 |
| ISSN | 08933952 |
| e-ISSN | 15300285 |
| DOI | 10.1038/modpathol.2017.55 |
| Journal | Modern Pathology |
| Issue Number | 10 |
| Volume Number | 30 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2017-06-30 |
| Access Restriction | Open |
| Subject Keyword | Journal: Modern Pathology Rosai-dorfman Disease Next-generation Sequencing |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pathology and Forensic Medicine |
