Title Clonality analysis of multifocal papillary thyroid carcinoma by using genetic profiles
Authors Lu, Zheming
Sheng, Jindong
Zhang, Yujie
Deng, Jianhua
Li, Yong
Lu, Aiping
Zhang, Juan
Yu, Huan
Zhang, Min
Xiong, Zikai
Yan, Hai
Diplas, Bill H.
Lu, Youyong
Liu, Baoguo
Affiliation Peking Univ Canc Hosp & Inst, Genet Lab, 52 Fucheng Rd, Beijing 100142, Peoples R China.
Peking Univ Canc Hosp & Inst, Dept Head & Neck Surg, 52 Fucheng Rd, Beijing 100142, Peoples R China.
Peking Univ Canc Hosp & Inst, Lab Anim Ctr, Key Lab Carcinogenesis & Translat Res, Minist Educ, 52 Fucheng Rd, Beijing 100142, Peoples R China.
Peking Univ Canc Hosp & Inst, Dept Pathol, Beijing 100142, Peoples R China.
Novogene Bioinformat Technol Co Ltd, 38 Xueqing Rd, Beijing, Peoples R China.
Genetron Hlth Inc, 8 Life Sci Pkwy, Beijing, Peoples R China.
Duke Univ, Med Ctr, Dept Pathol, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
Peking Univ Canc Hosp & Inst, Mol Oncol Lab, 52 Fucheng Rd, Beijing 100142, Peoples R China.
Duke Univ, Med Ctr, Dept Pathol, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
Liu, BG (reprint author), Peking Univ Canc Hosp & Inst, Dept Head & Neck Surg, Key Lab Carcinogenesis & Translat Res, Minist Educ, 52 Fucheng Rd, Beijing 100142, Peoples R China.
Lu, YY (reprint author), Peking Univ Canc Hosp & Inst, Mol Oncol Lab, Key Lab Carcinogenesis & Translat Res, Minist Educ, 52 Fucheng Rd, Beijing 100142, Peoples R China.
Keywords multifocality
papillary thyroid cancer
exome sequencing
clonal origin
tumour evolution
field cancerization
DISTINCT TUMOR FOCI
PROSTATE-CANCER
BLADDER-CANCER
BRAF MUTATION
ORIGIN
MICROCARCINOMA
SUPPORTS
REARRANGEMENTS
HETEROGENEITY
DIAMETER
Issue Date 2016
Publisher JOURNAL OF PATHOLOGY
Citation JOURNAL OF PATHOLOGY.2016,239,(1),72-83.
Abstract Papillary thyroid carcinoma (PTC) is the most common adult thyroid malignancy and often presents with multiple anatomically distinct foci within the thyroid, known as multifocal papillary thyroid carcinoma (MPTC). The widespread application of the next-generation sequencing technologies in cancer genomics research provides novel insights into determining the clonal relationship between multiple tumours within the same thyroid gland. For eight MPTC patients, we performed whole-exome sequencing and targeted region sequencing to identify the non-synonymous point mutations and gene rearrangements of distinct and spatially separated tumour foci. Among these eight MPTCs, completely discordant mutational spectra were observed in the distinct cancerous nodules of patients MPTC1 and 5, suggesting that these nodules originated from independent precursors. In another three cases (MPTC2, 6, and 8), the distinct MPTC foci of these patients had no other shared mutations except BRAFV600E, also indicating likely independent origins. Two patients (MPTC3 and 4) shared almost identical mutational spectra amongst their separate tumour nodules, suggesting a common clonal origin. MPTC patient 7 had seven cancer foci, of which two foci shared 66.7% of mutations, while the remaining cancer foci displayed no common non-synonymous mutations, indicating that MPTC7 has multiple independent origins accompanied by intraglandular disease dissemination. In this study, we found that 75% of MPTC cases arose as independent tumours, which supports the field cancerization hypothesis describing multiple malignant lesions. MPTC may also arise from intrathyroidal metastases from a single malignant clone, as well as multiple independent origins accompanied by intrathyroidal metastasis. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
URI http://hdl.handle.net/20.500.11897/434153
ISSN 0022-3417
DOI 10.1002/path.4696
Indexed SCI(E)
PubMed
Appears in Collections: 北京肿瘤医院

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