High Frequency of Loss of Heterozygosity in Imprinted, Compared with Nonimprinted, Genomic Regions in Follicular Thyroid Carcinomas and Atypical Adenomas

Sarquis, Marta; Weber, Frank; Shen, Lei; Broelsch, Christoph E.; Jhiang, Sissy; Zedenius, Jan; Frilling, Andrea; Eng, Charis

doi:10.1210/jc.2005-1880

Cited by 22 publications

(25 citation statements)

References 26 publications

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“…Overlapping values were found in some individual cases of FA and FCmi exhibiting unusually low and high levels of tpo expression respectively. This overlapping was consistent with recent data suggesting the existence of an adenoma-carcinoma sequence in which a subset of FA might predispose to malignant transformation (Vasko et al 2004, Sarquis et al 2006. The finding that tpo is significantly lower in FCwi than FCmi and higher in PCfv than PCc confirms the strong correlation between tpo expression and follicular differentiation.…”

Section: Discussionsupporting

confidence: 92%

Expression of tpo mRNA in thyroid tumors: quantitiative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes

Cristofaro¹,

Silvy²,

Lanteaume³

et al. 2006

Endocr Relat Cancer

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Expression of tpo mRNA in thyroid tumors: quantitiative PCR analysis and correlation with alterations of ret , Braf , ras and pax 8 genes AbstractImmunocytochemistry (ICC) of thyroid peroxidase (TPO) using the monoclonal antibody MoAb47 has been used as malignancy marker on thyroid fine needle aspiration. However, little is known about the fate of TPO in thyroid carcinoma. We performed a qualitative PCR (Q-PCR) analysis to measure the expression of variants of tpo mRNA in 13 normal tissue samples, 30 benign tumors (BT), 21 follicular carcinomas (FC), 20 classical papillary carcinomas (PCc), 12 follicular variants of papillary carcinomas (PCfv) and nine oncocytic carcinomas (OC). We also studied mutations involving the ras, Braf, ret or pax8 genes. Results of Q-PCR were closely correlated with those of ICC (P < 0:0001; R ¼ 0.59) and showed that overall tpo expression was lower in all carcinomas than in normal and BT (P < 0:05). The ratio tpo2 or tpo3 to tpo1 was inversed in follicular tumors. Genetic mutations were observed in 90% of PCc, 61.9% of FC, 41.7% of PCfv, 0% of OC and 10% in BT. pax8-ppar 1 rearrangement was correlated with qualitative changes in tpo mRNA (P < 0:01). These results confirmed the decrease of TPO expression in 97% of thyroid carcinomas regardless of histological type and the overexpression of shorter splice variants in follicular tumors. Both reduction in quantity of TPO and impairment of its maturation process could account for the atypical immunohistochemical reaction of MoAb47 with TPO.

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Section: Discussionsupporting

confidence: 92%

Expression of tpo mRNA in thyroid tumors: quantitiative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes

Cristofaro¹,

Silvy²,

Lanteaume³

et al. 2006

Endocr Relat Cancer

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“…Tumour-specific LOH is found in sporadic FTC, with and without oxyphilia, at both 19p13.2 and 2q21 (Stankov et al 2004). Another study found LOH at 14q32 in sporadic FTA (22%) and FTC (43%; Sarquis et al 2006). These findings suggest that tumour suppressor susceptibility genes lie in these chromosomal regions and that genetically inherited, or somatically acquired, disruptions of these genes may predispose to FNMTC initiation and/or progression.…”

Section: Introductionmentioning

confidence: 94%

Familial non-medullary thyroid carcinoma (FNMTC): analysis of fPTC/PRN, NMTC1, MNG1 and TCO susceptibility loci and identification of somatic BRAF and RAS mutations

Cavaco¹,

Batista²,

Martins³

et al. 2008

Endocrine Related Cancer

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Linkage analysis has identified four familial non-medullary thyroid carcinoma (FNMTC) susceptibility loci: fPTC/PRN (1p13.2-1q22), NMTC1 (2q21), MNG1 (14q32) and TCO (19p13.2). To date, there is no evidence for the involvement of genes from the RAS/RAF signalling pathway in FNMTC. The aim of our study was to evaluate the role of the four susceptibility loci, and RAS/RAF signalling pathway genes, in FNMTC. In total, 8 FNMTC families, and 27 thyroid lesions from family members (22 papillary thyroid carcinomas (PTCs): 11 classic, 10 of the follicular variant and 1 of the mixed variant; 4 follicular thyroid adenomas (FTAs) and 1 nodular goitre (NG)), were evaluated for the involvement of the four susceptibility regions, using linkage and loss of heterozygosity (LOH) analyses. BRAF and H-, N-and K-RAS mutations were also screened in the 27 lesions and patients. Linkage analysis in seven informative families showed no evidence for the involvement of any of the four candidate regions, supporting a genetic heterogeneity for FNMTC. Twenty tumours (74%), of which 18 were PTCs, showed no LOH at the four susceptibility loci. The remaining seven tumours (four PTCs, two FTAs and one NG) showed variable patterns of LOH. Fourteen tumours (52%) had somatic mutations: BRAF-V600E mutation was observed in 9 out of the 22 PTCs (41%); and H-RAS and N-RAS mutations were detected in 5 out of the 22 PTCs (23%). Our data suggest that the four candidate regions are not frequently involved in FNMTC and that the somatic activation of BRAF and RAS plays a role in FNMTC tumourigenesis.

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“…It has been suggested that the overall LOH in thyroid tumors more frequently affects the regions that are imprinted, i.e., those with parent-specific expression of genes, as compared to non-imprinted regions [177].…”

Section: Loss Of Heterozygositymentioning

confidence: 99%

Recent Developments in the Molecular Biology of the Thyroid

Nikiforov

2009

Endocrine Pathology:

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High Frequency of Loss of Heterozygosity in Imprinted, Compared with Nonimprinted, Genomic Regions in Follicular Thyroid Carcinomas and Atypical Adenomas

Cited by 22 publications

References 26 publications

Expression of tpo mRNA in thyroid tumors: quantitiative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes

Expression of tpo mRNA in thyroid tumors: quantitiative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes

Familial non-medullary thyroid carcinoma (FNMTC): analysis of fPTC/PRN, NMTC1, MNG1 and TCO susceptibility loci and identification of somatic BRAF and RAS mutations

Recent Developments in the Molecular Biology of the Thyroid

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