Identifying the clonal relationship model of multifocal papillary thyroid carcinoma by whole genome sequencing.
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.
Institute of Translational Medicine, Second Military Medical University, Shanghai 200433, PR China.
Mao
M
Xia
Department of Breast and Thyroid Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
Hengyu
H
Li
International Joint Cancer Institute, Second Military Medical University, Shanghai 200433, PR China.
Qian
Q
Ma
Institute of Translational Medicine, Second Military Medical University, Shanghai 200433, PR China.
Dong
D
Yu
Institute of Translational Medicine, Second Military Medical University, Shanghai 200433, PR China.
Jing
J
Li
Department of Medical Genetics, College of Basic Medical Science, Second Military Medical University, Shanghai 200433, PR China.
Yi
Y
Zhang
Department of Breast and Thyroid Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China. Electronic address: sheng528yuan@163.com.
Yuan
Y
Sheng
Institute of Translational Medicine, Second Military Medical University, Shanghai 200433, PR China. Electronic address: guoyingjun2017@163.com.
Yingjun
Y
Guo
D000328:Adult; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D002874:Chromosome Mapping / Q000379:methods; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
Clonal relationship; Multifocal papillary thyroid carcinoma; Multifocality; Whole genome sequencing