학술논문
Targeted next-generation sequencing of Japanese patients with sinonasal mucosal melanomas identifies frequent NRAS and CTNNB1 mutations.
Document Type
Academic Journal
Author
Tsushima N; Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. Electronic address: tsushima-na@huhp.hokudai.ac.jp.; Kano S; Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.; Hatanaka KC; Center for Development of Advanced Diagnostics, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Hokkaido, Japan.; Suzuki T; Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.; Hamada S; Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.; Idogawa H; Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.; Nakamaru Y; Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.; Suzuki M; Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.; Hatanaka Y; Center for Development of Advanced Diagnostics, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Hokkaido, Japan.; Homma A; Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
Source
Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 7708170 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1476 (Electronic) Linking ISSN: 03858146 NLM ISO Abbreviation: Auris Nasus Larynx Subsets: MEDLINE
Subject
Language
English
Abstract
Objective: Mucosal melanoma is a rare malignancy; however, the reported incidence rate of mucosal melanoma is higher in Asians than in Caucasians. Sinonasal mucosal melanoma (SNMM) is an aggressive malignancy with a poor prognosis due to distant metastasis. Systemic therapy with BRAF inhibitor and MEK inhibitor is one of the standards of care for cutaneous melanoma patients with BRAF V600 mutations. However, no molecular targeted therapy for patients with mucosal melanoma has been established. Relatively few studies have described the genetic mutations associated with mucosal melanoma because of its low frequency. Furthermore, to the best of our knowledge, the genetic mutations among Japanese patients have not been reported. Therefore, in the current study, we evaluated the genetic and clinicopathological characteristics of patients with SNMM.
Methods: A total of 18 tissue samples obtained from patients with SNMM were analyzed for genetic mutations based on targeted next-generation sequencing to investigate the driver of tumorigenesis and/or candidate genes for predicting clinical outcomes in SNMM. We also performed immunohistochemistry for patients identified with CTNNB1 mutations.
Results: Eight of the 18 (44 %) patients had genetic mutations. The most frequent mutation was NRAS (6/18, 33 %), followed by CTNNB1 (2/18, 11 %) and BRAF (1/18, 5.6 %). One patient had both NRAS and CTNNB1 mutations. Clinical outcomes did not differ significantly between those with and without genetic mutations. NRAS mutations were associated with relatively higher T classification and worse survival rates, although the differences were not significant. The nuclear translocation of β-catenin was detected in both tumors with CTNNB1 mutations. The amino acid change in the BRAF mutation was K601R in exon 15. In the current study, no BRAF V600 mutations were detected.
Conclusion: Genetic mutations were not significantly associated with clinical outcomes. However, NRAS mutations may be a prognostic predictor and CTNNB1 mutation may be a treatment effector for immune check inhibitors. A larger prospective study is required to clarify the clinical importance of genetic mutations in patients with SNMM.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest associated with this manuscript.
(Copyright © 2023. Published by Elsevier B.V.)
Methods: A total of 18 tissue samples obtained from patients with SNMM were analyzed for genetic mutations based on targeted next-generation sequencing to investigate the driver of tumorigenesis and/or candidate genes for predicting clinical outcomes in SNMM. We also performed immunohistochemistry for patients identified with CTNNB1 mutations.
Results: Eight of the 18 (44 %) patients had genetic mutations. The most frequent mutation was NRAS (6/18, 33 %), followed by CTNNB1 (2/18, 11 %) and BRAF (1/18, 5.6 %). One patient had both NRAS and CTNNB1 mutations. Clinical outcomes did not differ significantly between those with and without genetic mutations. NRAS mutations were associated with relatively higher T classification and worse survival rates, although the differences were not significant. The nuclear translocation of β-catenin was detected in both tumors with CTNNB1 mutations. The amino acid change in the BRAF mutation was K601R in exon 15. In the current study, no BRAF V600 mutations were detected.
Conclusion: Genetic mutations were not significantly associated with clinical outcomes. However, NRAS mutations may be a prognostic predictor and CTNNB1 mutation may be a treatment effector for immune check inhibitors. A larger prospective study is required to clarify the clinical importance of genetic mutations in patients with SNMM.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest associated with this manuscript.
(Copyright © 2023. Published by Elsevier B.V.)