title: Targeted DNA Sequencing Detects Mutations Related to Susceptibility among Familial Non-medullary Thyroid Cancer.
abstract: Some studies have demonstrated that familial non-medullary thyroid cancer (FNMTC) has a more aggressive clinical behavior compared to sporadic NMTC (SNMTC). However, FNMTC is difficult to differentiate from SNMTC by the morphology and immunohistochemistry. Although genes responsible for FNMTC were unclear, screening for rare germline mutations on known important tumor suppressor genes might offer more insights on predicting susceptibility to FNMTC. Here, a customized panel was designed to capture all exons of 31 cancer susceptive genes possibly related to FNMTC. Using next-generation sequencing we performed deep sequencing to achieve 500× coverage of the targeted regions. At the end 45 variants were identified in 29 of 47 familial patients and 6 of 16 sporadic patients. Notably, several germline mutations were found matching between paired FNMTC patients from the same family, including APC L292F and A2778S, BRAF D22N, MSH6 G355S and A36V, MSH2 L719F, MEN1 G508D, BRCA1 SS955S, BRCA2 G2508S, and a GNAS inframe insertion. We demonstrated a novel approach to help diagnose and elucidate the genetic cause of the FNMTC patients, and assess whether their family members are exposed to a higher genetic risk. The findings would also provide insights on monitoring the potential second cancers for thyroid cancer patients.
authors.affiliation: Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.
authors.forename: Li
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Li
authors.affiliation: Guangzhou Burning Rock Biotech, Guangzhou International Biotech Island (GIBI), Guangzhou 510300, China.
authors.forename: Shaokun
authors.initials: S
authors.lastname: Chuai
authors.affiliation: Guangzhou Burning Rock Biotech, Guangzhou International Biotech Island (GIBI), Guangzhou 510300, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Cancer Molecular Diagnosis Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Cancer Molecular Diagnosis Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: Cancer Molecular Diagnosis Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.
authors.forename: Jinpu
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.|Key Laboratory of Cancer Prevention and Therapy, Tianjin, Huanhuxi Road, Ti-Yuan-Bei, Hexi District, Tianjin 300060, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm