Lee Olivia W, Karyadi Danielle M, Hartley Stephen W, Zhou Weyin, Machiela Mitchell J, Zamani Shahriar A, Zurnadzhy Liudmyla Yu, Weinstein John N, Park Young Joo, Seo Jeong-Sun, Thomas Gerry A, Bogdanova Tetiana I, Tronko Mykola D, Morton Lindsay M, Chanock Stephen J
Eur Thyroid J. 2025 Jan 27;14(1). doi: 10.1530/ETJ-24-0235. Print 2025 Feb 1.
Deletion of the long q arm of chromosome 22 (22qDEL) is the most frequently identified recurrent somatic copy number alteration observed in papillary thyroid carcinoma (PTC). Since its role in PTC is not fully understood, we conducted a pooled analysis of genomic characteristics and clinical correlates in 1094 primary tumors from four published PTC genomic studies. The majority of PTC cases with 22qDEL exhibited arm-level loss of heterozygosity (86%); nearly all PTC cases with 22qDEL had losses in 22q12 and 13, which together constitute 70% of the q arm. Our analysis confirmed that 22qDEL occurs more frequently with RAS point mutations (50.4%), particularly HRAS (70.3%), compared with other PTC drivers (9.3%), supporting the conclusion that 22qDEL is unlikely to be a solitary driver of PTC but possibly an important co-factor in carcinogenesis, particularly in PTCs with RAS driver mutations. Differential RNA expression analyses revealed downregulation of most genes located on chromosome 22 in cases with 22qDEL compared to those without 22qDEL. Many differentially expressed genes are drawn from immune response and regulation pathways. These findings highlight the value of further investigations into the contributions of 22qDEL events to PTC, perhaps mediated through immune perturbations.
22号染色体长臂缺失（22qDEL）是在甲状腺乳头状癌（PTC）中最常发现的复发性体细胞拷贝数改变。由于其在PTC中的作用尚未完全了解，我们对四项已发表的PTC基因组研究中的1094例原发性肿瘤的基因组特征和临床相关性进行了汇总分析。大多数伴有22qDEL的PTC病例表现出臂水平的杂合性缺失（86%）；几乎所有伴有22qDEL的PTC病例在22q12和13区域都有缺失，这两个区域共同构成了q臂的70%。我们的分析证实，与其他PTC驱动因素（9.3%）相比，22qDEL与RAS点突变（50.4%），尤其是HRAS（70.3%）同时出现的频率更高，这支持了22qDEL不太可能是PTC的唯一驱动因素，但可能是致癌过程中的一个重要辅助因素，特别是在具有RAS驱动突变的PTC中。差异RNA表达分析显示，与无22qDEL的病例相比，有22qDEL的病例中位于22号染色体上的大多数基因表达下调。许多差异表达基因来自免疫反应和调节途径。这些发现凸显了进一步研究22qDEL事件对PTC的贡献的价值，这可能是通过免疫扰动介导的。
