<i>THADA‐IGF2BP3</i> fusions detected in fine‐needle aspiration specimens of thyroid nodules: An institutional experience

Gubbiotti, Maria A.; Andrianus, Stefen; Baloch, Zubair W.

doi:10.1002/dc.25113

Cited by 4 publications

(1 citation statement)

References 22 publications

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“…On the contrary, if suppressed, the immune response is triggered through the infiltration of CD8 + T cells and increased toxicity (89). In addition to this finding, the IGF2BP3-THADA fusion has been demonstrated to cause overexpression of the partner gene IGF2BP3, leading to sustained growth and invasion through the activation of PI3KCA and MAPK pathways (34,90). For its part, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is associated with a poor prognosis implicated in several mechanisms leading to aberrant metabolism in cancer (91).…”

Section: Spotlight Of Novel Therapies: Gene Fusionsmentioning

confidence: 99%

Drug repositioning in thyroid cancer: from point mutations to gene fusions

Sánchez-Marín,

Silva-Cázares,

González-Del Carmen

et al. 2024

Front. Oncol.

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The diagnosis of thyroid cancer (TC) has increased dramatically in recent years. Papillary TC is the most frequent type and has shown a good prognosis. Conventional treatments for TC are surgery, hormonal therapy, radioactive iodine, chemotherapy, and targeted therapy. However, resistance to treatments is well documented in almost 20% of all cases. Genomic sequencing has provided valuable information to help identify variants that hinder the success of chemotherapy as well as to determine which of those represent potentially druggable targets. There is a plethora of targeted therapies for cancer, most of them directed toward point mutations; however, chromosomal rearrangements that generate fusion genes are becoming relevant in cancer but have been less explored in TC. Therefore, it is relevant to identify new potential inhibitors for genes that are recurrent in the formation of gene fusions. In this review, we focus on describing potentially druggable variants and propose both point variants and fusion genes as targets for drug repositioning in TC.

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Section: Spotlight Of Novel Therapies: Gene Fusionsmentioning

confidence: 99%

Drug repositioning in thyroid cancer: from point mutations to gene fusions

Sánchez-Marín,

Silva-Cázares,

González-Del Carmen

et al. 2024

Front. Oncol.

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THADA‐IGF2BP3 gene fusions in thyroid fine needle aspiration is involved in the pathway to “noninvasive follicular thyroid neoplasm with papillary‐like nuclear features”

Zand,

Kim,

Rodriguez

et al. 2024

Diagnostic Cytopathology

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BackgroundThe increased usage and adaptation of molecular testing of thyroid fine needle aspirations (FNA) has expanded the variety and number of gene fusions identified. While the identified number of molecular alterations is increasing, the definitive association between preoperative molecular analysis and phenotype has yet to be established. The aim of this study was to examine Thyroid adenoma‐associated (THADA)‐IGF2BP3 molecular fusions with FNA categorization, surgical pathology diagnosis, and other molecular alterations detected by ThyroSeq Genomic Classifier testing.MethodsFNA cytology samples of thyroid nodules from 04/2017 to 01/2023 with the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS; Bethesda III) or follicular neoplasm suspicious for follicular neoplasm (FN/SFN; Bethesda IV) with associated ThyroSeqV3 testing were reviewed. Parameters including patient demographics, FNA diagnosis, ThyroSeq V3 results, and surgical pathology follow up were examined.Results87 out of 249 (35%) FNA specimens of thyroid nodules displayed molecular alterations. 64 cases (74%) had a cytology diagnosis of AUS and 23 (26%) had FN. RAS mutation was observed in 48 cases. On surgical follow‐up, 17 (35%) cases showed non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP), while 14 (29%) patients had a malignant diagnosis. THADA‐IGF2BP3 fusions were seen in 8 cases, all with NIFTP on surgical pathology follow‐up (100%).ConclusionsAnalysis of THADA‐IGF2BP3 fusion, in our institutional series, shows close association with NIFTP cases. THADA‐IGF2BP3 fusion, which seems to be a favorable prognostic indicator in general, may serve as a molecular marker for non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP).

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Molecular Markers in Follicular and Oncocytic Thyroid Carcinomas: Clinical Application of Molecular Genetic Testing

Belaiche,

Morand,

Turkdogan

et al. 2024

Current Oncology

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Background: Oncocytic thyroid carcinoma (OTC) was previously considered a variant of follicular thyroid carcinoma (FTC) but has recently been reclassified as a separate form of thyroid cancer. This study aimed to demonstrate that FTC and OTC are fundamentally distinct entities that can potentially be differentiated preoperatively through cytology and/or molecular testing. Methods: A retrospective chart review of patients diagnosed with FTC and OTC operated upon at two university health centers from January 2016 to September 2023 (n = 3219) was conducted. Molecular testing results were correlated with histopathologic diagnosis. Results: Fifty patients met the inclusion criteria. FTC was identified in 27 (54.0%) patients, and OTC in 23 (46.0%) patients. Patients with OTC were older (61.8 years) than FTC patients (51.2 years) (p = 0.013). Moreover, aggressive tumors were found in 39.1% (9/23) of OTCs compared to 11.1% (3/27) of FTCs (p = 0.021). Amongst Bethesda category III and IV nodules, 17 out of 20 (85.0%) OTC cytology reports demonstrated an oncocytic subtype compared to only 5 out of 24 FTC cytology reports (20.8%) (p = 0.002). On molecular testing, the EIF1AX alteration was exclusively present in OTCs while the PAX8/PPARy and PTEN alterations were exclusively found in FTCs. Copy number alterations (CNAs) were found to be more prevalent in OTC (66.7%) compared to FTC (33.3%), and they were not indicative of tumor aggressiveness. Within the OTC group, all three patients who had a TP53 alteration were diagnosed with aggressive cancer. Lastly, the OTCs exhibited a higher frequency of multiple alterations on molecular testing (66.7%) compared to FTCs (33.3%). Conclusion: To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC.

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THADA‐IGF2BP3 fusions detected in fine‐needle aspiration specimens of thyroid nodules: An institutional experience

Cited by 4 publications

References 22 publications

Drug repositioning in thyroid cancer: from point mutations to gene fusions

Drug repositioning in thyroid cancer: from point mutations to gene fusions

THADA‐IGF2BP3 gene fusions in thyroid fine needle aspiration is involved in the pathway to “noninvasive follicular thyroid neoplasm with papillary‐like nuclear features”

Molecular Markers in Follicular and Oncocytic Thyroid Carcinomas: Clinical Application of Molecular Genetic Testing

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