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Update on genetically defined lung neoplasms: NUT carcinoma and thoracic SMARCA4- deficient undifferentiated tumors
Virchows Archiv ( IF 3.4 ) Pub Date : 2021-01-06 , DOI: 10.1007/s00428-020-03011-3
Kyriakos Chatzopoulos , Jennifer M. Boland

NUT carcinoma, also known as NUT midline carcinoma, is an aggressive malignancy mainly affecting the midline structures of younger patients and almost invariably leading to death within a few months of the diagnosis. Morphologically, NUT carcinoma consists of sheets of monomorphous small or medium size cells with scant cytoplasm, commonly featuring areas of abrupt squamous differentiation with keratinization. Immunohistochemistry for NUT protein is sensitive and specific, typically showing a speckled nuclear reactivity, assisting in diagnosis. The molecular background of NUT carcinoma includes the reciprocal translocation t(15;19) leading to expression of the BRD4-NUT fusion transcript with oncogenic properties. Other less common genes may occasionally be fused with NUT not only in NUT carcinoma but also in other soft tissue tumors, highlighting the fact that NUT-rearranged tumors may represent a larger and more diverse family of neoplasms. Thoracic SMARCA4-deficient undifferentiated tumors are aggressive malignancies diagnosed more often in young male smokers, which often lead to death within a few months. SMARCA4-deficient tumors show undifferentiated morphology with occasional hepatoid and rhabdoid features. Immunohistochemically, the hallmark of diagnosis is loss of expression of SMARCA4 (BRG1). Concurrent loss of SMARCA2 expression, as well as expression of one or more stem cell markers SOX2, CD34, or SALL4 is common. Truncating mutations in SMARCA4, a catalytic subunit of the mammalian BAF (SWI/SNF) complex, are the dominant oncogenic molecular event underlying the pathogenesis of these tumors. SMARCA4 deficiency can also be seen as a passenger somatic event in multiple solid neoplasms manifesting as focal dedifferentiation and rhabdoid morphology.



中文翻译:

基因定义的肺肿瘤的最新进展:NUT癌和胸部SMARCA4缺陷的未分化肿瘤

NUT癌,也称为NUT中线癌,是一种侵袭性恶性肿瘤,主要影响年轻患者的中线结构,几乎总是在诊断后的几个月内导致死亡。从形态上讲,NUT癌由细胞质稀少的单形小或中型细胞片组成,通常具有突然的鳞状分化和角质化区域。NUT蛋白的免疫组织化学敏感且特异,通常表现出斑点的核反应性,有助于诊断。NUT癌的分子背景包括相互易位t(15; 19),导致表达具有致癌特性的BRD4-NUT融合转录本。其他不常见的基因有时可能会与NUT融合不仅在NUT癌中,而且在其他软组织肿瘤中,都突显了一个事实,即NUT重排的肿瘤可能代表了更大,更多样化的肿瘤家族。胸腔SMARCA4缺陷的未分化肿瘤是侵袭性恶性肿瘤,在年轻的男性吸烟者中更经常被诊断出,通常会在几个月内导致死亡。SMARCA4缺陷型肿瘤表现出未分化的形态,偶有肝样和横纹肌样特征。免疫组织化学诊断的标志是SMARCA4(BRG1)表达的丧失。SMARCA2表达以及一种或多种干细胞标记SOX2,CD34或SALL4的表达同时丧失是很常见的。SMARCA4中的截断突变,是哺乳动物BAF(SWI / SNF)复合体的催化亚基,是这些肿瘤发病机理的主要致癌分子事件。SMARCA4缺乏症也可以看作是多个实体瘤中的客运体细胞事件,表现为局灶性去分化和横纹肌样形态。

更新日期:2021-01-07
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