Abnormal transcripts of FHIT gene in thyroid cancer.

Chang, Tsan‐Kuo; Tsai, Tung-Lung; Wu, Ying-Ying; Yang, Hsiu-Ping; W, C; Yang, An Hang; Lee, C H

doi:10.3892/or.5.1.245

Cited by 4 publications

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“…The loss of Fhit protein in murine tumors was independent of tumor histology, similar to Fhit expression in human thyroid tumors (McIver et al, 2000). In this murine study however, Fhit loss progresses, consistent with the frequent loss of FHIT in late-stage poorly di erentiated human anaplastic thyroid carcinomas (Zou et al, 1999) but in contrast to reports of FHIT gene loss early in thyroid tumor development (Chang et al, 1998). The reason for these di erences is not clear but may involve species-or organ-speci®c di erences or disparities between the origin of the p53 and RET/ PTC3 mutations in these studies (transgenesis) compared to human disease (somatic mutation).…”

Section: Discussionsupporting

confidence: 82%

“…The possibility that genomic instability results from p53 gene loss suggested that other mutations might be induced by the loss of p53. We chose to investigate the loss of Fhit in thyroid tumors for three reasons: (i) Fhit is located in a chromosomal fragile site and may re¯ect genome wide changes (Glover et al, 1998); (ii) The human FHIT protein is lost in a majority of head and neck cancers, and mutations have been detected in both di erentiated and undi erentiated carcinomas of the thyroid (Chang et al, 1998;Virgilio et al, 1996;Zou et al, 1999);and (iii) No data exist relating coincident p53 and Fhit loss in thyroid cancer or their combined e ect on cancer progression. We ®nd high expression of Fhit in small carcinomas detected in young RET/PTC3 p537/7 mice (53 months old) but extensive loss in tumors derived from mice 46 months old, indicating that Fhit loss in this animal model is a late event.…”

Section: Discussionmentioning

confidence: 99%

“…Since dominant oncogenes often cooperate with mutant tumor suppressor genes to disrupt normal cellular growth, survival, and/or di erentiation, they are often co-expressed in cancer (Hunter, 1997). Accordingly, Tpr53 (p53) and FHIT tumor suppressor gene mutations have been found in both di erentiated and undi erentiated thyroid carcinomas (Chang et al, 1998;Duh and Grossman, 1995;Zou et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Altered gene expression in immunogenic poorly differentiated thyroid carcinomas from RET/PTC3p53−/− mice

Powell

Russell

et al. 2001

Oncogene

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Cancers develop and progress via activation of oncogenes and loss of tumor suppressor genes, a progression that can be recapitulated through cross breeding mouse strains harboring genetic mutations. To de®ne the role of RET/PTC3, p53 and Fhit in thyroid carcinogenesis, we intercrossed RET/PTC3 transgenics with p537/7 mice. This new strain, RET/PTC3 p537/7 , succumb to rapidly growing and strikingly large multilobed thyroid tumors containing mixtures of both well and poorly di erentiated, highly proliferative follicular epithelial cells. Interestingly, transplanted tumors from RET/ PTC3 p537/7 mice grew in SCID but not syngeneic immunocompetent mice indicating that these advanced tumors were immunogenic. RET/PTC3 protein expression was reduced to undetectable levels in tumors of older mice suggesting that the continued elevated expression of RET/PTC3 may not be necessary for tumor progression. Similarly, expression of Fhit protein was reduced in early tumors and undetected in older tumors irrespective of tumor histopathology. In contrast to RET/PTC3 p537/7 mice, RET/PTC3 Fhit7/7 mice did not develop advanced thyroid carcinomas. These studies support a model of human thyroid cancer whereby thyroid epithelium expresses RET/PTC3 protein at early stages of tumor development, followed by the reduction of RET/PTC3 and loss of p53 function with progressive reduction of Fhit protein expression coincident with malignant progression. Oncogene (2001) 20, 3235 ± 3246.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Altered gene expression in immunogenic poorly differentiated thyroid carcinomas from RET/PTC3p53−/− mice

Powell

Russell

et al. 2001

Oncogene

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“…2; Supplementary Table 4), including the wellknown tumour suppressor genes PTPRD (60%), FHIT (40%) and CDKN2A (30%). Several reports have shown previously that FHIT and CDKN2A are involved in thyroid tumourigenesis (Chang et al 1998, Elisei et al 1998, Zou et al 1999, Lee et al 2008, whereas the involvement of PTPRD in ATC is a novel finding. PTPRD encodes a receptor protein tyrosine phosphatase that is deleted in a wide range of tumours, such as neuroblastoma and glioblastoma; these deletions are believed to lead to STAT3 hyperactivation and thereby promote tumourigenesis (Molenaar et al 2012, Ortiz et al 2014.…”

Section: Discussionmentioning

confidence: 97%

Genomic complexity and targeted genes in anaplastic thyroid cancer cell lines

Woodward

Biloglav

Ravi

et al. 2017

Endocrine-Related Cancer

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Anaplastic thyroid cancer (ATC) is a highly malignant disease with a very short median survival time. Few studies have addressed the underlying somatic mutations, and the genomic landscape of ATC thus remains largely unknown. In the present study, we have ascertained copy number aberrations, gene fusions, gene expression patterns, and mutations in early-passage cells from ten newly established ATC cell lines using single nucleotide polymorphism (SNP) array analysis, RNA sequencing and whole exome sequencing. The ATC cell line genomes were highly complex and displayed signs of replicative stress and genomic instability, including massive aneuploidy and frequent breakpoints in the centromeric regions and in fragile sites. Loss of heterozygosity involving whole chromosomes was common, but there were no signs of previous near-haploidisation events or chromothripsis. A total of 21 fusion genes were detected, including six predicted in-frame fusions; none were recurrent. Global gene expression analysis showed 661 genes to be differentially expressed between ATC and papillary thyroid cancer cell lines, with pathway enrichment analyses showing downregulation of signalling as well as cell adhesion molecules in ATC. Besides previously known driver events, such as mutations in, , and the promoter, we identified and as putative novel target genes in ATC, based on deletions in six and four cell lines, respectively; the latter gene also carried a somatic mutation in one cell line. Taken together, our data provide novel insights into the tumourigenesis of ATC and may be used to identify new therapeutic targets.

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“…66 With complete sequencing of the FHIT gene, deletions between exons 2 and 9 were found in seven cases of thyroid tumors in Taiwan, suggesting that FHIT gene alterations may have a role in the formation of thyroid neoplasm. 67 …”

Section: Mutations Outside the Mapk Pathwaymentioning

confidence: 99%

A systematic review of genetic studies of thyroid disorders in Taiwan

Huang

Jap

2015

Journal of the Chinese Medical Association

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A systematic review of genetic studies of thyroid disorders in Taiwan identified studies of gene mutations involved in the synthesis and binding of thyroid hormone, as well as mutations of proto-oncogenes and tumor suppressor genes in thyroid cancer. Studies related to gene polymorphisms in patients with autoimmune thyroid disease (AITD) and thyroid cancer were also reviewed. The most prevalent mutations in the Han-Chinese population were c.2268insT in the thyroid peroxidase (TPO) gene and c.919-2A>G in the Pendred syndrome (PDS) gene. Additional mutations have also been revealed in the genes encoding TPO (n = 5), thyroglobulin (TG; n = 6), pendrin (n = 2), and thyroxine-binding globulin (TBG; n = 2), which were novel at the time they were reported. The prevalence of various somatic mutations in differentiated thyroid cancer was similar in Taiwan and Western countries, with the RAS kinase mutation and tyrosine receptor kinase (TRK) and rearranged during transfection (RET) proto-oncogenes being detected in lower frequencies and the B-type RAF kinase (BRAF) mutation accounting for the majority of cases. Recent microRNA analysis revealed an association between miR146b and the BRAF mutation, which was associated with poor prognosis of papillary thyroid carcinoma (PTC). Susceptibility to Graves' disease (GD) was linked to the human leukocyte antigen (HLA) region. The associated alleles were different in Han-Chinese and Caucasians; HLA-DPB1*0501, the major allele in Taiwan, has a low frequency in the West. By contrast, a high frequency of HLA-DRB1*0301 was detected in Caucasians but not Han-Chinese. In addition to the HLA region, cytotoxic T lymphocyte-associated molecule-4 (CTLA4) gene polymorphisms +49G>A and +6230G>A (CT60) were positively associated with GD. The GG genotype and G allele of single nucleotide polymorphism (SNP) +49G>A were also related to relapse of Graves' hyperthyroidism after antithyroid drug withdrawal. Differences in the genetic patterns between Han-Chinese and Caucasians for some thyroid disorders suggest the importance of variable genetic influences in different populations.

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Abnormal transcripts of FHIT gene in thyroid cancer.

Cited by 4 publications

References 0 publications

Altered gene expression in immunogenic poorly differentiated thyroid carcinomas from RET/PTC3p53−/− mice

Altered gene expression in immunogenic poorly differentiated thyroid carcinomas from RET/PTC3p53−/− mice

Genomic complexity and targeted genes in anaplastic thyroid cancer cell lines

A systematic review of genetic studies of thyroid disorders in Taiwan

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