Nadal Alfons, Cardesa Antonio, Agaimy Abbas, Almangush Alhadi, Franchi Alessandro, Hellquist Henrik, Leivo Ilmo, Zidar Nina, Ferlito Alfio
Pathology Department, Department of Clinical Fundamentals, Universitat de Barcelona, IDIBAPS, Clínic Barcelona, Barcelona, Spain.
Universitat de Barcelona, Barcelona, Spain.
Virchows Arch. 2024 Dec;485(6):965-976. doi: 10.1007/s00428-024-03987-2. Epub 2024 Nov 29.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is a cause of significant mortality and morbidity. The epidemiology of this cancer varies worldwide due to either genetic differences in populations or differences in carcinogen exposure. The application of massive parallel sequencing-based techniques in HNSCC should provide a helpful understanding of the genetic alterations that eventually lead to HNSCC development and progression, and ideally, could be used for personalized therapy. In this review, the reader will find an overview of the mutational profile of conventional HNSCC according to published results on massive parallel sequencing data that confirm the pivotal role of TP53 and the frequent involvement of CDKN2A and PIK3CA. The reader will also find a more detailed description of the genes, such as NOTCH1 and FBXW7, that were not identified in HNSCCs before the development of these techniques, the differences that can be site-specific, such as the different mutational signatures that indicate specific carcinogens for various subsites of the head and neck, and finally, the actionability of these findings that should allow more personalized therapy for patients.
头颈部鳞状细胞癌(HNSCC)是全球第六大常见癌症,是导致显著死亡率和发病率的一个原因。由于人群中的遗传差异或致癌物暴露差异,这种癌症的流行病学在全球范围内有所不同。基于大规模平行测序技术在HNSCC中的应用应有助于了解最终导致HNSCC发生和进展的基因改变,理想情况下,可用于个性化治疗。在这篇综述中,读者将根据已发表的大规模平行测序数据结果,找到传统HNSCC突变谱的概述,这些数据证实了TP53的关键作用以及CDKN2A和PIK3CA的频繁参与。读者还将找到对一些基因的更详细描述,如NOTCH1和FBXW7,这些基因在这些技术发展之前在HNSCC中未被发现,可能存在位点特异性差异,如不同的突变特征表明头颈部不同亚部位存在特定致癌物,最后,这些发现的可操作性应能为患者提供更个性化的治疗。