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Pal, Tuya; Hamel, Nancy; Vesprini, Danny; Sanders, Kevin; Mitchell, Margot; Quercia, Nada; Cheong, Nathalie Ng; Murray, Angus; Foulkes, William D.; Narod, Steven A.

doi:10.1023/a:1011541424424

Cited by 13 publications

(3 citation statements)

References 40 publications

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“…Among follicular thyroid cancer cases 2/42 harbored PTEN mutations [53]. Another study found no PTEN mutations in women presenting with both primary breast and thyroid cancers [54].…”

Section: Cancer/tumor Risksmentioning

confidence: 99%

PTEN Hamartoma Tumor Syndrome: A Clinical Overview

Pilarski

2019

Cancers

141

166

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The phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a grouping of related genetic disorders that has been linked to germline mutations in the PTEN gene. These disorders include Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome, adult Lhermitte–Duclos disease, and autism spectrum disorders associated with macrocephaly. The majority of the clinical information available on PHTS, however, is related to individuals diagnosed with CS. There is still much to be learned about this disorder, since diagnostic criteria for CS were only established in 1996, before the identification of the PTEN gene, and were based primarily on features seen in cases reported in the existing literature. More recently, however, data from several large series of patients have shown that a number of the clinical features associated with PTEN mutations are either more or less common than previously reported. In addition, we now know that only about 30–35% of patients meeting clinical diagnostic criteria for Cowden syndrome actually have a detectable PTEN mutation. Thus, our understanding of PTEN-related diseases and their management has evolved significantly over time. The United States National Comprehensive Cancer Network (NCCN) has produced and regularly updates practice guidelines which include clinical diagnostic criteria as well as guidelines for PTEN testing and management of patients with mutations. This review will summarize the overall literature on PHTS as well as recent findings which are broadening our understanding of this set of disorders.

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“…Among follicular thyroid cancer cases 2/42 harbored PTEN mutations [53]. Another study found no PTEN mutations in women presenting with both primary breast and thyroid cancers [54].…”

Section: Cancer/tumor Risksmentioning

confidence: 99%

PTEN Hamartoma Tumor Syndrome: A Clinical Overview

Pilarski

2019

Cancers

141

166

View full text Add to dashboard Cite

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“…A relationship between BC and benign thyroid disease has also been hypothesised ( 7 ), given the common iodine transport mechanism ( 8 , 9 ), prevalence of anti-thyroid peroxidase (TPO) autoantibodies in BC patients ( 10 , 11 , 12 ) and the role of thyroid hormone receptor B in BC ( 13 ). A non-syndromic monogenic disorder predisposing to breast and thyroid cancers has been postulated but has not, as yet, been identified ( 14 ). However, it is possible that this association may be explained by overlapping moderate- or low-penetrance breast-thyroid cancer genetic susceptibility loci ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Investigating the association of rs2910164 with cancer predisposition in an Irish cohort

McVeigh

Mulligan

McVeigh

et al. 2017

Endocrine Connections

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IntroductionMicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA–mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort.MethodsThe study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22.ResultsThe total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98–1.46), P = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18–2.14), P = 0.002).ConclusionThe rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort.

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“…CS/CLS is one of the plausible causes of primary thyroid and breast cancers; and the standardized incidence rate ratio of second primary cancers in research participants with thyroid cancer is increased to 5.83 per 10000 person-years (95% CI, 3.01 to 10.18) by PTEN mutations (Ngeow, et al 2014). However, PTEN germline mutations are responsible for only a small portion of participants who present with non-syndromic primary thyroid and breast cancers (Ngeow et al 2014; Pal, et al 2001). We hypothesize that germline mutations in genes other than PTEN, SDHx, PIK3CA, and AKT may explain the high rate of primary thyroid and breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Germline PARP4 mutations in patients with primary thyroid and breast cancers

Ikeda¹,

Kiyotani²,

Yew³

et al. 2015

Endocrine-Related Cancer

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Germline mutations in the PTEN gene, which cause Cowden syndrome (CS), are known to be one of the genetic factors for primary thyroid and breast cancers, however, PTEN mutations are found in only a small subset of research participants with non-syndrome breast and thyroid cancers. In this study, we aimed to identify germline variants that may be related to genetic risk of primary thyroid and breast cancers. Genomic DNAs extracted from peripheral blood of 14 PTEN-wild-type female research participants with primary thyroid and breast cancers were analyzed by whole-exome sequencing. Gene-based case control association analysis using the information of 406 Europeans obtained from the 1000 Genomes Project database identified 34 genes possibly associated with the phenotype with P<1.0×10−3. Among them, rare variants in the PARP4 gene were detected at significant high frequency (odds ratio = 5.2, P = 1.0×10−5). The variants, G496V and T1170I, were found in 6 of the 14 study participants (43%) while their frequencies were only 0.5% in controls. Functional analysis using HCC1143 cell line showed that knockdown of PARP4 with siRNA significantly enhanced the cell proliferation, compared with the cells transfected with siControl (P = 0.02). Kaplan-Meier analysis using GEO, EGA and TCGA datasets showed poor progression-free survival (P = 0.006, Hazard ratio 0.71) and overall survival (P < 0.0001, Hazard ratio 0.79) in a PARP4 low-expression group, suggesting that PARP4 may function as a tumor suppression. In conclusion, we identified PARP4 as a possible susceptibility gene of primary thyroid and breast cancer.

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Untitled

Cited by 13 publications

References 40 publications

PTEN Hamartoma Tumor Syndrome: A Clinical Overview

PTEN Hamartoma Tumor Syndrome: A Clinical Overview

Investigating the association of rs2910164 with cancer predisposition in an Irish cohort

Germline PARP4 mutations in patients with primary thyroid and breast cancers

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