Institute of Translational Medicine, Second Military Medical University, Shanghai 200433, PR China.
Department of Breast and Thyroid Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
Cancer Lett. 2017 Jun 28;396:110-116. doi: 10.1016/j.canlet.2017.03.012. Epub 2017 Mar 14.
To evaluate the application of whole genome sequencing (WGS) in determining the inter-foci clonal relationship of multifocal papillary thyroid carcinoma (mPTC).
After reviewing PTC patient profiles, 8 cancer foci and germline control samples from 3 mPTC patients were analyzed by WGS. Single nucleotide variations (SNVs), copy number variation (CNV), structural variation and mutational signature were examined.
The multifocality rate of PTC was 35.1% and mPTC were shown to have larger primary tumor diameter, higher rate of lymph node metastasis and less number of accompanying non-cancerous lesions than single PTC in one or both gender groups. Out of the 8 cancer foci, 5 foci were identified as clonal-independent model with the rest 3 foci as clonal-derived model according to exonic SNVs spectrum. Non-exonic mutations provided compelling evidence at the genome-wide level for the classification. Specific CNV and 12 mutational signatures were also identified.
WGS could be an impressive tool in clonal relationship determination of PTC by providing a panoramic view of genome-wide somatic mutations. The substantial sequencing data provided additional information that could help studying the mechanism of carcinogenesis.
评估全基因组测序（WGS）在确定多灶性甲状腺乳头状癌（mPTC）病灶间克隆关系中的应用。
在回顾 PTC 患者特征后，对 3 例 mPTC 患者的 8 个癌灶和种系对照样本进行 WGS 分析。检测单核苷酸变异（SNV）、拷贝数变异（CNV）、结构变异和突变特征。
PTC 的多灶性发生率为 35.1%，与单发 PTC 相比，mPTC 患者的原发肿瘤直径更大，淋巴结转移率更高，伴随的非癌性病变数量更少，无论在男性还是女性群体中均如此。在 8 个癌灶中，5 个病灶被鉴定为克隆独立模型，其余 3 个病灶为克隆衍生模型，依据外显子 SNV 谱。非外显子突变在全基因组水平上为分类提供了有力证据。还鉴定了特定的 CNV 和 12 个突变特征。
WGS 可以通过提供全基因组体细胞突变的全景视图，成为确定 PTC 克隆关系的有效工具。大量的测序数据提供了额外的信息，有助于研究致癌机制。
