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SalvGlandDx- 一种全面的唾液腺癌种特异性下一代测序 panel,有助于诊断和确定治疗靶点。

SalvGlandDx - a comprehensive salivary gland neoplasm specific next generation sequencing panel to facilitate diagnosis and identify therapeutic targets.

机构信息

Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland.

Department of Pathology, Cantonal Hospital of Lucerne, Lucerne, Switzerland.

出版信息

Neoplasia. 2021 May;23(5):473-487. doi: 10.1016/j.neo.2021.03.008. Epub 2021 Apr 18.

Abstract

Diagnosis of salivary gland neoplasms is often challenging due to their high morphological diversity and overlaps. Several recurrent molecular alterations have been described recently, which can serve as powerful diagnostic tools and potential therapeutic targets (e.g. NTRK or RET fusions). However, current sequential molecular testing can be expensive and time consuming. In order to facilitate the diagnosis of salivary gland neoplasms, we designed an all-in-one RNA-based next generation sequencing panel suitable for the detection of mutations, fusions and gene expression levels (including NR4A3) of 27 genes involved in salivary gland neoplasms. Here we present the validation of the "SalvGlandDx" panel on FFPE histological specimen including fine needle aspiration (FNA) cell block material, against the standard methods currently used at our institution. In a second part we describe selected unique cases in which the SalvGlandDx panel allowed proper diagnosis and new insights into special molecular characteristics of selected salivary gland tumors. We characterize a unique salivary gland adenocarcinoma harboring a ZCCHC7-NTRK2 fusion, a highly uncommon spindle cell and pseudoangiomatoid adenoid-cystic carcinoma with MYBL1-NFIB fusion, and a purely oncocytic mucoepidermoid carcinoma, whereas diagnosis could be made by detection of a CRTC3-MAML2 rearrangement on the cell block specimen of the FNA. Further, a rare case of a SS18-ZBTB7A rearranged low-grade adenocarcinoma previously described as potential spectrum of microsecretory adenocarcinoma, is reported. In addition, features of six cases within the spectrum of polymorphous adenocarcinoma / cribriform adenocarcinoma of salivary gland including PRKD1 p.E710D mutations and novel fusions involving PRKAR2A-PRKD1, SNX9-PRKD1 and ATL2-PRKD3, are described.

摘要

由于唾液腺肿瘤具有高度的形态多样性和重叠性,因此其诊断常常具有挑战性。最近描述了几种常见的分子改变,这些改变可作为强大的诊断工具和潜在的治疗靶点(例如,NTRK 或 RET 融合)。然而,目前的连续分子检测可能既昂贵又耗时。为了促进唾液腺肿瘤的诊断,我们设计了一种基于 RNA 的一站式下一代测序 panel,适用于检测与唾液腺肿瘤相关的 27 个基因的突变、融合和基因表达水平(包括 NR4A3)。在此,我们展示了“SalvGlandDx”panel 在 FFPE 组织学标本(包括细针穿刺(FNA)细胞块材料)上的验证结果,与我们机构目前使用的标准方法进行了对比。在第二部分中,我们描述了一些选定的独特病例,这些病例中,SalvGlandDx panel 可进行正确诊断,并为选定的唾液腺肿瘤的特殊分子特征提供新的见解。我们描述了一个独特的唾液腺癌,其携带 ZCCHC7-NTRK2 融合;一个高度罕见的梭形细胞和假血管瘤样腺样囊性癌,具有 MYBL1-NFIB 融合;一个纯粹的嗜酸性黏液表皮样癌,通过在 FNA 的细胞块标本中检测到 CRTC3-MAML2 重排,即可进行诊断。此外,报告了一例罕见的 SS18-ZBTB7A 重排的低度腺癌,该病例先前被描述为微分泌性腺癌的潜在谱系。此外,还描述了 6 例多形性腺癌/筛状腺癌谱内的病例特征,包括 PRKD1 p.E710D 突变和涉及 PRKAR2A-PRKD1、SNX9-PRKD1 和 ATL2-PRKD3 的新融合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/629f/8081865/41fd315d30cb/gr1.jpg

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