Hatchett William John, Brunetti Marta, Andersen Kristin, Tandsæther Maren Randi, Lobmaier Ingvild, Lund-Iversen Marius, Lien-Dahl Thomas, Micci Francesca, Panagopoulos Ioannis
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Pathol Oncol Res. 2024 Jan 22;30:1611553. doi: 10.3389/pore.2024.1611553. eCollection 2024.
Intramuscular myxomas are benign tumors that are challenging to diagnose, especially on core needle biopsies. Acquired chromosomal aberrations and pathogenic variants in codon 201 or codon 227 in GNAS complex locus gene () have been reported in these tumors. Here we present our genetic findings in a series of 22 intramuscular myxomas. The tumors were investigated for the presence of acquired chromosomal aberrations using G-banding and karyotyping. Pathogenic variants in codon 201 or codon 227 of were assessed using direct cycle Sanger sequencing and Ion AmpliSeq Cancer Hotspot Panel v2 methodologies. Eleven tumors carried chromosomal abnormalities. Six tumors had numerical, four had structural, and one had both numerical and structural chromosomal aberrations. Gains of chromosomes 7 and 8 were the most common abnormalities being found in five and four tumors respectively. Pathogenic variants in were detected in 19 myxomas (86%) with both methodologies. The detected pathogenic variants were p.R201H in nine cases (seven with abnormal and two with normal karyotypes), p.R201C in five cases, all with normal karyotypes, p.R201S in three cases (two with abnormal and one with normal karyotype), p.R201G in one case with a normal karyotype, and p.Q227E in one case with a normal karyotype. Firstly, our data indicate a possible association between chromosomal abnormalities and pathogenic variants in intramuscular myxomas. Secondly, the presence of the rare pathogenic variants R201S, p.R201G and p.Q227E in 26% (5 out of 19) of myxomas with pathogenic variants shows that methodologies designed to detect only the common "hotspot" of p.R201C and p.R201H will give false negative results. Finally, a comparison between Ion AmpliSeq Cancer Hotspot Panel v2 and direct cycle Sanger sequencing showed that direct cycle Sanger sequencing provides a quick, reliable, and relatively cheap method to detect pathogenic variants, matching even the most cutting-edge sequencing methods.
肌内黏液瘤是一种诊断具有挑战性的良性肿瘤，尤其是在粗针活检时。这些肿瘤中已报道存在获得性染色体畸变以及GNAS复合位点基因（）第201密码子或第227密码子的致病变异。在此，我们展示了对22例肌内黏液瘤的遗传学研究结果。通过G显带和核型分析对肿瘤进行获得性染色体畸变检测。采用直接循环桑格测序法和Ion AmpliSeq癌症热点区域Panel v2方法评估第201密码子或第227密码子的致病变异。11例肿瘤存在染色体异常。6例为数目异常，4例为结构异常，1例同时存在数目和结构染色体畸变。7号和8号染色体的增加是最常见的异常，分别在5例和4例肿瘤中发现。两种方法在19例（86%）黏液瘤中均检测到致病变异。检测到的致病变异包括9例p.R201H（7例核型异常，2例核型正常）、5例p.R201C（均为核型正常）、3例p.R201S（2例核型异常，1例核型正常）、1例核型正常的p.R201G以及1例核型正常的p.Q227E。首先，我们的数据表明肌内黏液瘤中染色体异常与致病变异之间可能存在关联。其次，在19例有致病变异的黏液瘤中，26%（5/19）存在罕见致病变异R201S、p.R201G和p.Q227E，这表明仅设计用于检测常见“热点”p.R201C和p.R201H的方法会得出假阴性结果。最后，Ion AmpliSeq癌症热点区域Panel v2与直接循环桑格测序的比较表明，直接循环桑格测序提供了一种快速、可靠且相对便宜的检测致病变异的方法，甚至可与最前沿的测序方法相媲美。
