■唾液腺肿瘤是罕见的肿瘤。多形性腺瘤(PA)是最常见的良性病变。肌上皮癌(MECA)是罕见的恶性肿瘤,但预后不利。这项研究的目的是确定可能导致原发性根治性PA切除患者动态MECA进展的遗传重排。
■在2例患者的原发和复发肿瘤组织中进行了1500个基因编码序列的下一代测序(NGS)。最初诊断为PA,并在一年内检测到多灶性MECA。福尔马林固定的石蜡包埋块与肿瘤组织进行NGS分析,涉及小规模突变,以及局灶性和染色体臂水平的拷贝数变化。
■这项研究显示PA和MECA组织中的FGFR2基因突变,从两个病人身上获得。其中一个,致病性突变p.Pro253Arg,与对注册药物抑制剂的敏感性有关。此外,FGFR1,EGFR,和CDK4/CDK6扩增,以及CDKN2A/B缺失,在一个案例中被发现。此外,检测到抑制基因APC2和PIK3C2A的突变,但仅限于MECA组织。分析还确定了以下染色体拷贝改变:4q12-q13.3、9p21.3、5q23.1-q34、del8p23.3-p12和del13q21.31-q31。
■FGFR2基因重排,在我们两名患者的原发性PA和MECAexPA样本中鉴定,可能是恶性转化和疾病进展的原因。鼓励进一步的研究,以证实研究结果的相关性。FGFR2抑制剂的治疗选择可考虑在具有证实的FGFR2突变的晚期或转移性MECAexPA中。
UNASSIGNED: Salivary gland tumours are rare neoplasms. Pleomorphic adenoma (PA) is the most frequent benign lesion. Myoepithelial carcinoma (MECA) is rarely recognized malignancy, but the prognosis is unfavourable. The aim of this study was to identify genetic rearrangements that might be responsible for dynamic MECA progression in patients with primary radical PA excision.
UNASSIGNED: Next-generation sequencing (NGS) of 1500 gene coding sequences was performed in primary and recurrent tumour tissue collected from 2 patients, in whom PA was initially diagnosed and within one year multifocal MECA was detected. Formalin-fixed paraffin-embedded blocks with tumour tissues were subject to NGS analysis, involving small-scale mutations, as well as focal and chromosomal arm-level copy number changes.
UNASSIGNED: This study showed mutations in the FGFR2 gene in PA and MECA tissues, obtained from both patients. One of them, pathogenic mutation p.Pro253Arg, was associated with sensitivity to registered drug inhibitors. Additionally, FGFR1, EGFR, and CDK4/CDK6 amplification, as well as CDKN2A/B deletion, were detected in one case. Furthermore, mutations in suppressor gene APC2 and PIK3C2A were detected, but only in MECA tissue. The analysis also identified the following chromosomal copy alterations: 4q12-q13.3, 9p21.3, 5q23.1-q34, del8p23.3-p12, and del13q21.31-q31.1.
UNASSIGNED: Rearrangement of the FGFR2 gene, identified in primary PA and MECA ex PA samples of both our patients, may be responsible for the malignant transformation and the disease progression. Further studies are encouraged to confirm the relevance of the findings. The therapy option with FGFR2 inhibitors may be considered in advanced or metastatic MECA ex PA with confirmed FGFR2 mutations.