Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis

Han Luo; Xue Liao; Yun Qin; Qianqian Hou; Zhinan Xue; Yang Liu; Yang Liu; Feiyang Shen; Yuelan Wang; Yong Jiang; Linlin Song; Linlin Song; Haining Chen; Lingyun Zhang; Lingyun Zhang; Tao Wei; Lunzhi Dai; Li Yang; Wei Zhang; Zhihui Li; Heng Xu; Heng Xu; Jingqiang Zhu; Yang Shu; Yang Shu

doi:10.3389/fonc.2021.620924

Frontiers in Oncology (Jun 2021)

Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis

Han Luo,
Xue Liao,
Yun Qin,
Qianqian Hou,
Zhinan Xue,
Yang Liu,
Yang Liu,
Feiyang Shen,
Yuelan Wang,
Yong Jiang,
Linlin Song,
Linlin Song,
Haining Chen,
Lingyun Zhang,
Lingyun Zhang,
Tao Wei,
Lunzhi Dai,
Li Yang,
Wei Zhang,
Zhihui Li,
Heng Xu,
Heng Xu,
Jingqiang Zhu,
Yang Shu,
Yang Shu

Affiliations

Han Luo: Department of Thyroid and Parathyroid Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
Xue Liao: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
Yun Qin: Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
Qianqian Hou: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
Zhinan Xue: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
Yang Liu: Department of Thyroid and Parathyroid Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
Yang Liu: West China School of Medicine, Sichuan University, Chengdu, China
Feiyang Shen: West China School of Medicine, Sichuan University, Chengdu, China
Yuelan Wang: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
Yong Jiang: Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
Linlin Song: Department of Thyroid and Parathyroid Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
Linlin Song: West China School of Medicine, Sichuan University, Chengdu, China
Haining Chen: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
Lingyun Zhang: Department of Thyroid and Parathyroid Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
Lingyun Zhang: West China School of Medicine, Sichuan University, Chengdu, China
Tao Wei: Department of Thyroid and Parathyroid Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
Lunzhi Dai: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
Li Yang: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
Wei Zhang: Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, Changsha, China
Zhihui Li: Department of Thyroid and Parathyroid Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
Heng Xu: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
Heng Xu: Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
Jingqiang Zhu: Department of Thyroid and Parathyroid Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
Yang Shu: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
Yang Shu: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China

DOI: https://doi.org/10.3389/fonc.2021.620924
Journal volume & issue: Vol. 11

Abstract

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BackgroundBrain metastasis is extremely rare but predicts dismal prognosis in papillary thyroid cancer (PTC). Dynamic evaluation of stepwise metastatic lesions was barely conducted to identify the longitudinal genomic evolution of brain metastasis in PTC.MethodChronologically resected specimen was analyzed by whole exome sequencing, including four metastatic lymph nodes (lyn 1–4) and brain metastasis lesion (BM). Phylogenetic tree was reconstructed to infer the metastatic pattern and the potential functional mutations.ResultsContrasting with lyn1, ipsilateral metastatic lesions (lyn2–4 and BM) with shared biallelic mutations of TSC2 indicated different genetic originations from multifocal tumors. Lyn 3/4, particularly lyn4 exhibited high genetic similarity with BM. Besides the similar mutational compositions and signatures, shared functional mutations (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

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