The utility of DNA methylation profiling in the diagnosis of un-, de- and trans-differentiated melanoma: a series of 11 cases.

IF 3.9 2区 医学 Q2 CELL BIOLOGY
Histopathology Pub Date : 2024-09-02 DOI:10.1111/his.15309
Zeynep Betul Erdem, Baptiste Ameline, Judith V M G Bovée, Hester van Boven, Daniel Baumhoer, John S A Chrisinger, Karen J Fritchie
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引用次数: 0

Abstract

Aims: Melanomas are recognised for their remarkable morphological plasticity. Some tumours may lose conventional features and/or acquire non-melanocytic characteristics, referred to as undifferentiated, dedifferentiated and transdifferentiated melanoma. Despite this phenotypical variability, melanomas typically maintain their cancer driver aberrations, affecting genes such as BRAF, NRAS and NF1. Currently, little is known about whether the DNA methylation profile follows the loss or change of differentiation or is retained despite extensive morphological transformation.

Methods and results: In this study we analysed 11 melanoma cases, comprising six males and five females, with a median age of 67 years, including five undifferentiated, four trans-differentiated and two de-differentiated melanomas. Undifferentiated and trans-differentiated tumours either arose in a patient with known melanoma and/or presented in the groin/axilla with molecular alterations consistent with melanoma. Cases with heterologous differentiation resembled chondrosarcoma, osteosarcoma, angiosarcoma and rhabdomyosarcoma both morphologically and immunohistochemically, while undifferentiated tumours resembled undifferentiated pleomorphic sarcoma. Methylome profiling was performed, and unsupervised clustering analysis revealed nine cases (five undifferentiated, three trans-differentiated and one de-differentiated) to cluster closely together with conventional melanomas from a reference set. Two cases clustered separately with a distinct group of conventional melanomas exhibiting H3K27me3 loss.

Conclusions: Despite loss of differentiation and phenotypical plasticity, methylation patterns seem to be retained in undifferentiated, de-differentiated and trans-differentiated melanomas and represent useful diagnostic tools to enhance diagnostic precision in these diagnostically challenging cases.

DNA 甲基化图谱在诊断未分化、去分化和经分化黑色素瘤中的应用:11 例系列病例。
目的:黑色素瘤具有显著的形态可塑性。一些肿瘤可能会失去传统特征和/或获得非黑色素细胞特征,被称为未分化、去分化和转分化黑色素瘤。尽管表型存在差异,但黑色素瘤通常会保持其癌症驱动基因畸变,影响 BRAF、NRAS 和 NF1 等基因。目前,人们对 DNA 甲基化概况是随着分化的丧失或改变而改变,还是在广泛的形态学转变后仍被保留知之甚少:在这项研究中,我们分析了 11 例黑色素瘤病例,其中男性 6 例,女性 5 例,中位年龄为 67 岁,包括 5 例未分化黑色素瘤、4 例经分化黑色素瘤和 2 例去分化黑色素瘤。未分化和经分化的肿瘤要么出现在已知患有黑色素瘤的患者身上,要么出现在腹股沟/腋窝,且分子改变与黑色素瘤一致。异源分化的病例在形态学和免疫组化上与软骨肉瘤、骨肉瘤、血管肉瘤和横纹肌肉瘤相似,而未分化肿瘤则与未分化多形性肉瘤相似。进行了甲基组图谱分析,无监督聚类分析显示,9个病例(5个未分化、3个经分化和1个去分化)与参考集中的传统黑色素瘤紧密聚类。两个病例与一组表现出H3K27me3缺失的传统黑色素瘤单独聚类:尽管黑色素瘤失去了分化和表型的可塑性,但甲基化模式似乎在未分化、去分化和跨分化黑色素瘤中得以保留,是提高这些诊断难题病例诊断精确度的有用诊断工具。
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来源期刊
Histopathology
Histopathology 医学-病理学
CiteScore
10.20
自引率
4.70%
发文量
239
审稿时长
1 months
期刊介绍: Histopathology is an international journal intended to be of practical value to surgical and diagnostic histopathologists, and to investigators of human disease who employ histopathological methods. Our primary purpose is to publish advances in pathology, in particular those applicable to clinical practice and contributing to the better understanding of human disease.
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