Original ArticleIdentifying the clonal relationship model of multifocal papillary thyroid carcinoma by whole genome sequencing

•The incidence rate of multifocality reached 35% in our cohort consisting of 920 PTC patients.•Multifocal PTC presented unique clinicopathological characteristics including higher preference for lymph node metastasis.•Both clonal-independent and clonal-derived model were identified in the 8 cancer foci studied.•Non-exonic mutations could play a critical role in clonal relationship analysis.•Whole genome sequencing additionally offered crucial information about the molecular genetic characteristics of cancer.

PurposeTo evaluate the application of whole genome sequencing (WGS) in determining the inter-foci clonal relationship of multifocal papillary thyroid carcinoma (mPTC).MethodsAfter 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.ResultsThe 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.ConclusionsWGS 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.