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https://doi.org/10.1530/ERC-14-0537
Title: | Germline and somatic SDHx alterations in apparently sporadic differentiated thyroid cancer | Authors: | Ni, Y Seballos, S Ganapathi, S Gurin, D Fletcher, B Ngeow, J Nagy, R Kloos, R.T Ringel, M.D LaFramboise, T Eng, C |
Keywords: | protein SDHx protein unclassified drug membrane protein SDHB protein, human SDHC protein, human SDHD protein, human succinate dehydrogenase adult aged Article breast adenocarcinoma cancer staging carcinogenesis chromosome 1 chromosome duplication comparative study controlled study copy number variation differentiated thyroid cancer female gene gene expression gene loss genetic association genetic variability germline mutation human invasive carcinoma major clinical study male middle aged sdhx gene somatic mutation thyroid carcinoma thyroid follicular carcinoma adenocarcinoma breast tumor carcinoma genetics mutation Paget nipple disease thyroid tumor very elderly Adenocarcinoma, Follicular Adult Aged Aged, 80 and over Breast Neoplasms Carcinoma Carcinoma, Ductal, Breast Female Genetic Variation Humans Membrane Proteins Middle Aged Mutation Succinate Dehydrogenase Thyroid Neoplasms |
Issue Date: | 2015 | Publisher: | BioScientifica Ltd. | Citation: | Ni, Y, Seballos, S, Ganapathi, S, Gurin, D, Fletcher, B, Ngeow, J, Nagy, R, Kloos, R.T, Ringel, M.D, LaFramboise, T, Eng, C (2015). Germline and somatic SDHx alterations in apparently sporadic differentiated thyroid cancer. Endocrine-Related Cancer 22 (2) : 121-130. ScholarBank@NUS Repository. https://doi.org/10.1530/ERC-14-0537 | Rights: | Attribution 4.0 International | Abstract: | Along with breast and endometrial cancers, thyroid cancer is a major component cancer in Cowden syndrome (CS). Germline variants in SDHB/C/D (SDHx) genes account for subsets of CS/CS-like cases, conferring a higher risk of breast and thyroid cancers over those with only germline PTEN mutations. To investigate whether SDHx alterations at both germline and somatic levels occur in apparently sporadic breast cancer and differentiated thyroid cancer (DTC), we analyzed SDHx genes in the following four groups: i) 48 individuals with sporadic invasive breast adenocarcinoma for germline mutation; ii) 48 (expanded to 241) DTC for germline mutation; iii) 37 pairs DTC tumor-normal tissues for germline and somatic mutation and mRNA expression levels; and iv) data from 476 patients in the Cancer Genome Atlas thyroid carcinoma dataset for validation. No germline SDHx variant was found in a pilot series of 48 breast cancer cases. As germline SDHx variants were found in our pilot of 48 thyroid cancer cases, we expanded to three series of DTC comprising a total 754 cases, and found 48 (6%) with germline SDHx variants (P<0.001 compared with 0/350 controls). In 513 tumors, we found 27 (5%) with large somatic duplications within chromosome 1 encompassing SDHC. Both papillary and follicular thyroid tumors showed consistent loss of SDHC/D gene expression (P<0.001), which is associated with earlier disease onset and higher pathological-TNM stage. Therefore, we conclude that both germline and somatic SDHx mutations/variants occur in sporadic DTC but are very rare in sporadic breast cancer, and overall loss of SDHx gene expression is a signature of DTC. © 2015 The authors. | Source Title: | Endocrine-Related Cancer | URI: | https://scholarbank.nus.edu.sg/handle/10635/180118 | ISSN: | 1351-0088 | DOI: | 10.1530/ERC-14-0537 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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