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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Identifying the clonal relationship model of multifocal papillary thyroid carcinoma by whole genome sequencing.
Cancer Letters 2017 June 29
PURPOSE: To evaluate the application of whole genome sequencing (WGS) in determining the inter-foci clonal relationship of multifocal papillary thyroid carcinoma (mPTC).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
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