Please use this identifier to cite or link to this item: https://doi.org/10.1530/ERC-14-0537
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dc.titleGermline and somatic SDHx alterations in apparently sporadic differentiated thyroid cancer
dc.contributor.authorNi, Y
dc.contributor.authorSeballos, S
dc.contributor.authorGanapathi, S
dc.contributor.authorGurin, D
dc.contributor.authorFletcher, B
dc.contributor.authorNgeow, J
dc.contributor.authorNagy, R
dc.contributor.authorKloos, R.T
dc.contributor.authorRingel, M.D
dc.contributor.authorLaFramboise, T
dc.contributor.authorEng, C
dc.date.accessioned2020-10-26T07:03:25Z
dc.date.available2020-10-26T07:03:25Z
dc.date.issued2015
dc.identifier.citationNi, 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
dc.identifier.issn1351-0088
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/180118
dc.description.abstractAlong 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.
dc.publisherBioScientifica Ltd.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectprotein
dc.subjectSDHx protein
dc.subjectunclassified drug
dc.subjectmembrane protein
dc.subjectSDHB protein, human
dc.subjectSDHC protein, human
dc.subjectSDHD protein, human
dc.subjectsuccinate dehydrogenase
dc.subjectadult
dc.subjectaged
dc.subjectArticle
dc.subjectbreast adenocarcinoma
dc.subjectcancer staging
dc.subjectcarcinogenesis
dc.subjectchromosome 1
dc.subjectchromosome duplication
dc.subjectcomparative study
dc.subjectcontrolled study
dc.subjectcopy number variation
dc.subjectdifferentiated thyroid cancer
dc.subjectfemale
dc.subjectgene
dc.subjectgene expression
dc.subjectgene loss
dc.subjectgenetic association
dc.subjectgenetic variability
dc.subjectgermline mutation
dc.subjecthuman
dc.subjectinvasive carcinoma
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectmiddle aged
dc.subjectsdhx gene
dc.subjectsomatic mutation
dc.subjectthyroid carcinoma
dc.subjectthyroid follicular carcinoma
dc.subjectadenocarcinoma
dc.subjectbreast tumor
dc.subjectcarcinoma
dc.subjectgenetics
dc.subjectmutation
dc.subjectPaget nipple disease
dc.subjectthyroid tumor
dc.subjectvery elderly
dc.subjectAdenocarcinoma, Follicular
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectBreast Neoplasms
dc.subjectCarcinoma
dc.subjectCarcinoma, Ductal, Breast
dc.subjectFemale
dc.subjectGenetic Variation
dc.subjectHumans
dc.subjectMembrane Proteins
dc.subjectMiddle Aged
dc.subjectMutation
dc.subjectSuccinate Dehydrogenase
dc.subjectThyroid Neoplasms
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1530/ERC-14-0537
dc.description.sourcetitleEndocrine-Related Cancer
dc.description.volume22
dc.description.issue2
dc.description.page121-130
dc.published.statePublished
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