Fluorescence in situ hybridization analysis using PAX8- and PPARG-specific probes reveals the presence of PAX8-PPARG translocation and 3p25 aneusomy in follicular thyroid neoplasms

Chia, Wai Kit; Na, Sharifah; Reena, Rahayu Md Zin; Zakaria, Zubaidah; Clarence-Ko, Ching Huat; Muhammad, Rohaizak; Ibrahim, Normala; Das, Srijit; Abdullah, Noor Hisham; Asmiati, A.; Rafie, Kaslan

doi:10.1016/j.cancergencyto.2009.08.001

Cited by 18 publications

(9 citation statements)

References 30 publications

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“…Other groups did not find PAX8 ⁄ PPARG rearrangements in FHCC or FHCA (Tables 3 and 4). [28][29][30][31][32][33][34] The absence of PAX8 ⁄ PPARG rearrangements in FHCC has been used to support the assumption that FHCC may develop via separate molecular events compared with non-FHCC, and may thus represent a distinct type of thyroid neoplasm. 32,33 Our results show that PAX8 ⁄ P-PARG rearrangements, which are particularly prevalent in FTA, FTC, and FVPTC, 16,31,34,35 can also be present in FHCC.…”

Section: Discussionmentioning

confidence: 99%

“…Summary of published studies of RET ⁄ PTC rearrangements, PAX8 ⁄ PPARG and ⁄ or PPARG rearrangements and BRAF, NRAS, HRAS and KRAS mutations in follicular Hü rthle cell tumours: follicular Hü rthle cell adenomas (FHCAs), follicular Hü rthle cell carcinomas (FHCCs), and papillary Hü rthle cell carcinomas (PHCCs)9,10,16,[24][25][26][28][29][30][31][32][33][34][38][39][40]42,[45][46][47][48][49]52 …”

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confidence: 99%

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RET/PTC rearrangement is prevalent in follicular Hürthle cell carcinomas

Vries¹,

Celestino²,

Castro³

et al. 2012

Histopathology

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

RET/PTC rearrangement is prevalent in follicular Hürthle cell carcinomas

Vries¹,

Celestino²,

Castro³

et al. 2012

Histopathology

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“…Congenital hypothyroidism is caused by several genetic defects and among these there are mutations in the PAX8 gene [1], [11], [12]. In addition to hypothyroidism, PAX8 plays a role also in the progression of follicular thyroid carcinomas and adenomas [13], [14]. In tissues other than the thyroid, PAX8 was found overexpressed in epithelial ovarian cancer [15] and it has been hypothesized that PAX8 maybe an important regulator of telomerase activity and cell survival in some gliomas [16].…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Pax8 Targets in FRTL-5 Thyroid Cells by Gene Silencing and Expression Microarray Analysis

et al. 2011

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BackgroundThe differentiation program of thyroid follicular cells (TFCs), by far the most abundant cell population of the thyroid gland, relies on the interplay between sequence-specific transcription factors and transcriptional coregulators with the basal transcriptional machinery of the cell. However, the molecular mechanisms leading to the fully differentiated thyrocyte are still the object of intense study. The transcription factor Pax8, a member of the Paired-box gene family, has been demonstrated to be a critical regulator required for proper development and differentiation of thyroid follicular cells. Despite being Pax8 well-characterized with respect to its role in regulating genes involved in thyroid differentiation, genomics approaches aiming at the identification of additional Pax8 targets are lacking and the biological pathways controlled by this transcription factor are largely unknown.Methodology/Principal FindingsTo identify unique downstream targets of Pax8, we investigated the genome-wide effect of Pax8 silencing comparing the transcriptome of silenced versus normal differentiated FRTL-5 thyroid cells. In total, 2815 genes were found modulated 72 h after Pax8 RNAi, induced or repressed. Genes previously reported to be regulated by Pax8 in FRTL-5 cells were confirmed. In addition, novel targets genes involved in functional processes such as DNA replication, anion transport, kinase activity, apoptosis and cellular processes were newly identified. Transcriptome analysis highlighted that Pax8 is a key molecule for thyroid morphogenesis and differentiation.Conclusions/SignificanceThis is the first large-scale study aimed at the identification of new genes regulated by Pax8, a master regulator of thyroid development and differentiation. The biological pathways and target genes controlled by Pax8 will have considerable importance to understand thyroid disease progression as well as to set up novel therapeutic strategies.

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“…In the last 7 years, the discoveries of recurrent gene fusions, such as TMPRSS2-ETS in prostate cancer, have 53,54 opened up new avenues for cancer research and treatment. The data summarized in this review indicate that the pathogenetic mechanisms involved in epithelial cancer may be similar to those known to operate in hematological and soft-tissue malignancies; these functional gene fusions may therefore serve as ideal diagnostic markers, provide insight into tumor biology, and most importantly, serve as specific therapeutic targets.…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

Morphologic Features of Carcinomas With Recurrent Gene Fusions

et al. 2012

Advances in Anatomic Pathology

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Recurrent gene fusions have been thought to play a central role in leukemias, lymphomas, and sarcomas, but they have been neglected in carcinomas, largely because of technical limitations of cytogenetics. In the past few years, an increasing number of recurrent gene fusions have been recognized in epithelial cancers. The majority of prostate cancers, for example, have an androgen-regulated fusion of one of the ETS transcription factor gene family. Notably, the fusion genes can often serve as specific diagnostic markers, criteria of molecular classification and therefore potential therapeutic targets. Recent studies have focused on investigations of morphologic features (phenotype) of recurrent gene fusions (genotype) in malignancies. In this review, we will summarize the histologic features of known recurrent genomic rearrangements in carcinomas, especially focusing on TMPRSS2-ERG fusion in prostate cancer, EML4-ALK in lung cancer, ETV6-NTRK3 in secretory breast cancer, RET/PTC and PAX8/PPARγ1 rearrangements in thyroid cancer. In addition, we will describe how these features could potentially be used to alert the pathologists of the diagnosis of fusion-positive tumor. A combination of histologic validation with other screening strategies (eg, immunohistochemistry) for recognition of recurrent gene fusions is also highlighted.

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Fluorescence in situ hybridization analysis using PAX8- and PPARG-specific probes reveals the presence of PAX8-PPARG translocation and 3p25 aneusomy in follicular thyroid neoplasms

Cited by 18 publications

References 30 publications

RET/PTC rearrangement is prevalent in follicular Hürthle cell carcinomas

RET/PTC rearrangement is prevalent in follicular Hürthle cell carcinomas

Identification of Novel Pax8 Targets in FRTL-5 Thyroid Cells by Gene Silencing and Expression Microarray Analysis

Morphologic Features of Carcinomas With Recurrent Gene Fusions

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