Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13058-016-0758-5
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dc.titlePatient survival and tumor characteristics associated with CHEK2:p.I157T - findings from the Breast Cancer Association Consortium
dc.contributor.authorMuranen, T.A
dc.contributor.authorBlomqvist, C
dc.contributor.authorDörk, T
dc.date.accessioned2020-11-10T07:52:34Z
dc.date.available2020-11-10T07:52:34Z
dc.date.issued2016
dc.identifier.citationMuranen, T.A, Blomqvist, C, Dörk, T (2016). Patient survival and tumor characteristics associated with CHEK2:p.I157T - findings from the Breast Cancer Association Consortium. Breast Cancer Research 18 (1) : 98. ScholarBank@NUS Repository. https://doi.org/10.1186/s13058-016-0758-5
dc.identifier.issn14655411
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/183312
dc.description.abstractBackground: P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival and characteristics of breast tumors of germ line p.I157T carriers. Methods: We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models. Additionally, we explored the p.I157T-associated genomic gene expression profile using data from breast tumors of 183 Finnish female breast cancer patients (ten p.I157T carriers) (GEO: GSE24450). Differential gene expression analysis was performed using a moderated t test. Functional enrichment was investigated using the DAVID functional annotation tool and gene set enrichment analysis (GSEA). The tumors were classified into molecular subtypes according to the St Gallen 2013 criteria and the PAM50 gene expression signature. Results: P.I157T was not associated with increased risk of early death, breast cancer-associated death or distant metastasis relapse, and there was a significant difference in prognosis associated with the two CHEK2 mutations, p.I157T and c.1100delC. Furthermore, p.I157T was associated with lobular histological type and clinico-pathological markers of good prognosis, such as ER and PR expression, low TP53 expression and low grade. Gene expression analysis suggested luminal A to be the most common subtype for p.I157T carriers and CDH1 (cadherin 1) target genes to be significantly enriched among genes, whose expression differed between p.I157T and non-carrier tumors. Conclusions: Our analyses suggest that there are fundamental differences in breast tumors of CHEK2:p.I157T and c.1100delC carriers. The poor prognosis associated with c.1100delC cannot be generalized to other CHEK2 mutations. @ 2016 The Author(s).
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectcadherin
dc.subjectcadherin 1
dc.subjectcheckpoint kinase 2
dc.subjectestrogen receptor
dc.subjectprogesterone receptor
dc.subjectprotein p53
dc.subjectunclassified drug
dc.subjectcheckpoint kinase 2
dc.subjectcodon
dc.subjecttranscriptome
dc.subjecttumor marker
dc.subjectadult
dc.subjectaged
dc.subjectArticle
dc.subjectbreast cancer
dc.subjectcancer grading
dc.subjectcancer mortality
dc.subjectcancer prognosis
dc.subjectcancer recurrence
dc.subjectcancer survival
dc.subjectCHEK2 gene
dc.subjectclinical feature
dc.subjectcontrolled study
dc.subjectdistant metastasis
dc.subjectfemale
dc.subjectFinn (citizen)
dc.subjectgene expression profiling
dc.subjectgene mutation
dc.subjectheterozygote
dc.subjecthistology
dc.subjecthuman
dc.subjecthuman tissue
dc.subjectmajor clinical study
dc.subjectprotein expression
dc.subjectamino acid substitution
dc.subjectbreast tumor
dc.subjectcancer staging
dc.subjectcluster analysis
dc.subjectcodon
dc.subjectepidemiology
dc.subjectEurope
dc.subjectgenetic association study
dc.subjectgenetics
dc.subjectmetastasis
dc.subjectmissense mutation
dc.subjectmortality
dc.subjectpathology
dc.subjectprognosis
dc.subjectAmino Acid Substitution
dc.subjectBiomarkers, Tumor
dc.subjectBreast Neoplasms
dc.subjectCheckpoint Kinase 2
dc.subjectCluster Analysis
dc.subjectCodon
dc.subjectEurope
dc.subjectFemale
dc.subjectGene Expression Profiling
dc.subjectGenetic Association Studies
dc.subjectHeterozygote
dc.subjectHumans
dc.subjectMutation, Missense
dc.subjectNeoplasm Grading
dc.subjectNeoplasm Metastasis
dc.subjectNeoplasm Staging
dc.subjectPrognosis
dc.subjectTranscriptome
dc.typeArticle
dc.contributor.departmentSURGERY
dc.description.doi10.1186/s13058-016-0758-5
dc.description.sourcetitleBreast Cancer Research
dc.description.volume18
dc.description.issue1
dc.description.page98
dc.published.statePublished
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