Analysis of head and neck carcinoma progression reveals novel and relevant stage-specific changes associated with immortalisation and malignancy

Head and neck squamous cell carcinoma (HNSCC) is a widely prevalent cancer globally with high mortality and morbidity. We report here changes in the genomic landscape in the development of these tumours from potentially premalignant lesions (PPOLS) to malignancy and lymph node metastases. Frequent likely pathological mutations are restricted to a relatively small set of genes including TP53, CDKN2A, FBXW7, FAT1, NOTCH1 and KMT2D; these arise early in tumour progression and are present in PPOLs with NOTCH1 mutations restricted to cell lines from lesions that subsequently progressed to HNSCC. The most frequent genetic changes are of consistent somatic copy number alterations (SCNA). The earliest SCNAs involved deletions of CSMD1 (8p23.2), FHIT (3p14.2) and CDKN2A (9p21.3) together with gains of chromosome 20. CSMD1 deletions or promoter hypermethylation were present in all of the immortal PPOLs and occurred at high frequency in the immortal HNSCC cell lines (promoter hypermethylation ~63%...

头颈部鳞状细胞癌（Head and neck squamous cell carcinoma, HNSCC）是全球范围内高发的恶性肿瘤，具有较高的死亡率和发病率。本文报道了此类肿瘤从潜在癌前病变（potentially premalignant lesions, PPOLS）进展为恶性肿瘤及淋巴结转移过程中的基因组图谱变化。常见的潜在致病性突变局限于相对较少的一组基因，包括TP53、CDKN2A、FBXW7、FAT1、NOTCH1和KMT2D；这些突变在肿瘤进展早期出现，并存在于PPOLS中，其中NOTCH1突变仅见于后续进展为HNSCC的病变细胞系。最常见的遗传改变是一致性的体细胞拷贝数变异（somatic copy number alterations, SCNA）。最早出现的SCNA包括CSMD1（8p23.2）、FHIT（3p14.2）和CDKN2A（9p21.3）的缺失，以及20号染色体的扩增。CSMD1缺失或启动子高甲基化存在于所有永生化PPOL细胞系中，并在永生化HNSCC细胞系中高频发生（启动子高甲基化发生率约63%...