Genetic heterogeneity displayed by tumour cells (intratumoural heterogeneity, ITH) represents a diagnostic challenge when assessing tumour mutational profile. In oral squamous cell carcinoma (OSCC), ITH may be found both in tumour cells and in adjacent mucosa. Genetic heterogeneity of the adjacent mucosa can be interpreted as evidence of the field cancerization (field heterogeneity, FH). The aim of the study was to investigate the impact of intratumoural and intrafield heterogeneity on locoregional control. Ten OSCC patients (5 recurrent and 5 nonrecurrent) were studied. Multiple areas were sampled from the bulk of the tumour and the adjacent nonneoplastic mucosa. A panel of 10 tumour-specific OSCC driver genes was analysed for each sample and was used to calculate heterogeneity. Values were compared among recurrent and nonrecurrent OSCC. Mutational analysis highlighted that a single tumour sample has limited accuracy in assessing the genetic profiles of tumours. High values of ITH considering shared mutations between specimens were found in both recurrent and non-recurrent OSCC (p = 0.095). On the contrary, the intrafield genetic heterogeneity was significantly less frequently in the non-recurrent OSCC group (p = 0.032). Heterogeneity within each specimen calculated with variant allele frequency confirmed that there was better discrimination between recurrent and nonrecurrent groups using nonneoplastic adjacent mucosa than tumour tissue (p value 0.0006 and 0.0048 respectively). In agreement with the theory of field cancerization, intrafield genetic heterogeneity correlates with a higher risk of developing loco-regional recurrences and second primaries. In order to reduce the ITH effects, analysis of multiple tumour areas should be encouraged.

中文翻译：

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口腔鳞状细胞癌的场内异质性对预后的影响。

当评估肿瘤突变情况时，肿瘤细胞显示的遗传异质性（肿瘤内异质性，ITH）代表了诊断挑战。在口腔鳞状细胞癌（OSCC）中，可能在肿瘤细胞和邻近的粘膜中都发现了ITH。相邻粘膜的遗传异质性可以解释为田间癌变的证据（田间异质性，FH）。该研究的目的是调查肿瘤内和场内异质性对局部区域控制的影响。研究了10例OSCC患者（5例复发和5例非复发）。从肿瘤的大部分和邻近的非肿瘤性粘膜取样多个区域。对每个样品分析一组10个肿瘤特异性OSCC驱动基因，并用于计算异质性。比较了复发性和非复发性OSCC的值。突变分析强调，单个肿瘤样本在评估肿瘤的遗传特征方面准确性有限。在复发性和非复发性OSCC中均发现考虑到标本之间共有突变的ITH值较高（p = 0.095）。相反，在非复发性OSCC组中，场内遗传异质性的频率明显降低（p = 0.032）。用变异等位基因频率计算的每个标本中的异质性证实，与肿瘤组织相比，使用非肿瘤性邻近粘膜更好地区分了复发组和非复发组（分别为p值0.0006和0.0048）。与田间癌变的理论相一致，田间遗传异质性与发生局部区域复发和第二原发性疾病的较高风险相关。