Muzza Marina, Pogliaghi Gabriele, Persani Luca, Fugazzola Laura, Colombo Carla
Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, 20095 Milan, Italy.
Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, 20095 Milan, Italy.
J Clin Med. 2021 Jun 16;10(12):2645. doi: 10.3390/jcm10122645.
Despite its potential clinical impact, intra-tumor genetic heterogeneity (ITH) has been scantly investigated in papillary thyroid cancer (PTC). We studied ITH in PTC by combining, for the first time, data derived from the evaluation of the normalized allelic frequencies (NAF) of the mutation/s, using a customized MassARRAY panel, and those obtained by the HUMARA clonality assay. Among tumors with a single mutation, 80% of cases with NAF 50 ± 5% were clonal, consistent with the presence of a single mutated clone, while 20% of cases showed a polyclonal pattern, suggesting the presence of the same mutation in two or more clones. Differently, all cases with NAF < 45% were polyclonal. Among tumors with double mutation, cases with both mutations showing NAF 50 ± 5% were monoclonal, consistent with the presence of a single clone harboring both mutations. On the other hand, all cases with double mutation at NAF < 45% were polyclonal, indicating the presence of two clones with different mutations. Finally, no significant differences in the clinico-pathological characteristics were found between monoclonal and polyclonal tumors. In conclusion, the present study adds insights into the concept of ITH in PTC, which warrants attention because the occurrence of this phenomenon is likely to affect the response to targeted drugs.
尽管具有潜在的临床影响，但甲状腺乳头状癌（PTC）中的肿瘤内基因异质性（ITH）却鲜有研究。我们首次通过结合使用定制的MassARRAY检测板评估突变的标准化等位基因频率（NAF）所获得的数据以及通过HUMARA克隆性检测获得的数据，对PTC中的ITH进行了研究。在仅有一个突变的肿瘤中，NAF为50±5%的病例中有80%是克隆性的，这与单一突变克隆的存在一致，而20%的病例表现出多克隆模式，表明在两个或更多克隆中存在相同的突变。不同的是，所有NAF<45%的病例都是多克隆的。在有两个突变的肿瘤中，两个突变的NAF均为50±5%的病例是单克隆的，这与存在一个同时携带两个突变的克隆一致。另一方面，所有NAF<45%的双突变病例都是多克隆的，表明存在两个具有不同突变的克隆。最后，单克隆和多克隆肿瘤在临床病理特征上未发现显著差异。总之，本研究为PTC中ITH的概念提供了新的见解，这种现象的发生可能会影响对靶向药物的反应，因此值得关注。
