Dataset Information

Primary mucosal melanomas of the head and neck are characterised by overexpression of the DNA mutating enzyme APOBEC3B.

ABSTRACT:

Aims

Primary head/neck mucosal melanomas (MMs) are rare and exhibit aggressive biologic behaviour and elevated mutational loads. The molecular mechanisms responsible for high genomic instability observed in head/neck MMs remain elusive. The DNA cytosine deaminase APOBEC3B (A3B) constitutes a major endogenous source of mutation in human cancer. A3B-related mutations are identified through C-to-T/-G base substitutions in 5'-TCA/T motifs. Herein, we present immunohistochemical and genomic data supportive of a role for A3B in head/neck MMs.

Methods and results

A3B protein levels were assessed in oral (n = 13) and sinonasal (n = 13) melanomas, and oral melanocytic nevi (n = 13) by immunohistochemistry using a custom rabbit α-A3B mAb (5210-87-13). Heterogeneous, selective-to-diffuse, nuclear only, A3B immunopositivity was observed in 12 of 13 (92.3%) oral melanomas (H-score range = 9-72, median = 40) and 8 of 13 (62%) sinonasal melanomas (H-score range = 1-110, median = 24). Two cases negative for A3B showed prominent cytoplasmic staining consistent with A3G. A3B protein levels were significantly higher in oral and sinonasal MMs than intraoral melanocytic nevi (P < 0.0001 and P = 0.0022, respectively), which were A3B-negative (H-score range = 1-8, median = 4). A3B levels, however, did not differ significantly between oral and sinonasal tumours (P > 0.99). NGS performed in 10 sinonasal MMs revealed missense NRAS mutations in 50% of the studied cases and one each KIT and HRAS mutations. Publicly available whole-genome sequencing (WGS) data disclosed that the number of C-to-T mutations and APOBEC3 enrichment score were markedly elevated in head/neck MMs (n = 2).

Conclusion

The above data strongly indicate a possible role for the mutagenic enzyme A3B in head/neck melanomagenesis, but not benign melanocytic neoplasms.

SUBMITTER: Argyris PP

PROVIDER: S-EPMC10107945 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Primary mucosal melanomas of the head and neck are characterised by overexpression of the DNA mutating enzyme APOBEC3B.

Argyris Prokopios P PP Naumann Jordan J Jarvis Matthew C MC Wilkinson Peter E PE Ho Dan P DP Islam Mohammed N MN Bhattacharyya Indraneel I Gopalakrishnan Rajaram R Li Faqian F Koutlas Ioannis G IG Giubellino Alessio A Harris Reuben S RS

Histopathology 20221205 4

<h4>Aims</h4>Primary head/neck mucosal melanomas (MMs) are rare and exhibit aggressive biologic behaviour and elevated mutational loads. The molecular mechanisms responsible for high genomic instability observed in head/neck MMs remain elusive. The DNA cytosine deaminase APOBEC3B (A3B) constitutes a major endogenous source of mutation in human cancer. A3B-related mutations are identified through C-to-T/-G base substitutions in 5'-TCA/T motifs. Herein, we present immunohistochemical and genomic d ...[more]

PMID: 36416305

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Project description:BackgroundHead and neck mucosal melanoma (HNMM) is defined as a rare malignant tumor derived from melanocytes. There is no consensus regarding the treatment protocol for HNMM in elderly patients.MethodsThe National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify elderly patients diagnosed with HNMM from 1975 to 2016. The chi-squared test was used to compare patient characteristics. The reverse Kaplan-Meier method was used to estimate the median follow-up time. The Kaplan-Meier method and log-rank test were used to estimate and compare the overall survival (OS) and disease-specific survival (DSS) of the groups. Cox regression analysis was used to evaluate the risk factors for OS and DSS of HNMM.ResultsOur retrospective study included 828 elderly patients with HNMM, and the 5-year OS and DSS rates were 22.4% and 27.4%, respectively. After adjusting for other variables in multivariate analysis, patients undergoing radiotherapy alone had worse OS [hazard ratio (HR) =1.449, 95% confidence interval (CI): 1.010-1.742, P=0.006] and DSS (HR =1.656, 95% CI: 1.257-2.181, P<0.001) than those undergoing surgery alone. No significant difference in OS (HR =0.892, 95% CI: 0.753-1.056, P=0.183) or DSS (HR =0.917, 95% CI: 0.764-1.101, P=0.354) was observed for patients undergoing surgery with or without radiotherapy. Our analysis of the subgroup of patients with complete clinical staging information demonstrated that the effects of surgery alone on OS (HR =0.734, 95% CI: 0.562-0.958, P=0.023) were inferior to those of surgery with radiotherapy, but no significant difference was noted compared with radiotherapy alone.ConclusionsThe survival of elderly patients with HNMM is increased with the combination of surgery and radiotherapy compared with surgery alone and radiotherapy alone. In addition, the population-based analysis demonstrated that combination therapy exhibited an obviously increased usage rate from 1975 to 2016, representing a mainstream treatment modality.

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Dataset Information

Primary mucosal melanomas of the head and neck are characterised by overexpression of the DNA mutating enzyme APOBEC3B.

Aims

Methods and results

Conclusion

Publications

Primary mucosal melanomas of the head and neck are characterised by overexpression of the DNA mutating enzyme APOBEC3B.

Similar Datasets

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