Mouse Model of Poorly Differentiated Thyroid Carcinoma Driven by STRN-ALK Fusion

Nikitski, Alyaksandr V.; Rominski, Susan L.; Wankhede, Mamta; Kelly, Lori A.; Panebianco, Federica; Barila, Guillermo; Altschuler, Daniel L.; Nikiforov, Yuri E.

doi:10.1016/j.ajpath.2018.07.012

Cited by 16 publications

(13 citation statements)

References 60 publications

(16 reference statements)

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“…To the best of our knowledge, there has been no articles reviewing diseases with STRN-ALK fusion genes across organs. A summary of the case series and case reports of tumors with STRN-ALK is presented in the Table . The oncogenic property of the STRN-ALK fusion gene was demonstrated by the presence of thyroid cancer in a mouse model expressing the STRN-ALK fusion gene [19]. Furthermore, deletion of the coiled-coil domain of STRN or mutation in the tyrosine kinase domain of ALK leads to absence of protein expression, and the presence of mutation in the tyrosine kinase sequence does not lead to carcinogenesis [20].…”

Section: Molecular Tumor Boardmentioning

confidence: 99%

A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review

et al. 2021

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Recently, several malignant peritoneal mesotheliomas (MPMs), occurring in young women without asbestos exposure and with fusion genes such as anaplastic lymphoma kinase (ALK) and Ewing sarcoma breakpoint region 1, have been reported. In the present case, we encountered MPM with STRN‐ALK fusion in a 17‐year‐old female adolescent. The case did not respond to chemotherapy and is currently in a clinical trial of alectinib. This is the fourth reported case of MPM with STRN‐ALK fusion. Of the 45 cancer cases with STRN‐ALK fusion in which the fusion partners were examined, all cases except for the current case showed fusion of exon 3 of STRN and exon 20 of ALK. This is the first case with fusion of exon 2 of STRN and exon 20 of ALK. Further advances in cancer genomic medicine may help clarify the clinical significance of this new fusion. Key Points Malignant peritoneal mesotheliomas (MPMs) can occur in young women without asbestos exposure and show fusion genes that activate anaplastic lymphoma kinase (ALK) by gene rearrangement. ALK rearrangement and the fusion partner can be detected by companion diagnostics and by next generation sequencing. Patients with MPMs with ALK rearrangement may benefit from target therapy.

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Section: Molecular Tumor Boardmentioning

confidence: 99%

A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review

et al. 2021

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“…Additionally, the chromosomal rearrangement of the ALK gene to various partners leads to a constitutive activation of ALK tyrosine kinase and represents a carcinogenic mechanism found in various cancer type including non-small-cell lung cancer and thyroid cancer [129]. In thyroid cancers, ALK fusions, most frequently the STRN-ALK fusion, are detected in PTC and, with higher frequency, in PDTC and ATC.…”

Section: Targeting Gene Rearrangements In Thyroid Cancermentioning

confidence: 99%

“…In thyroid cancers, ALK fusions, most frequently the STRN-ALK fusion, are detected in PTC and, with higher frequency, in PDTC and ATC. The crucial role of the STRN-ALK fusion in the development of dedifferentiated thyroid cancer have been highlighted by the development of a transgenic mouse model with phenotypic features recapitulating a poor differentiated human tumor [129].…”

Section: Targeting Gene Rearrangements In Thyroid Cancermentioning

confidence: 99%

Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses

Gheysen

Saussez

Journé

2020

Cells

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Accounting for about 2% of cancers diagnosed worldwide, thyroid cancer has caused about 41,000 deaths in 2018. Despite significant progresses made in recent decades in the treatment of thyroid cancer, many resistances to current monotherapies are observed. In our complete review, we report all treatments that were tested in combination against thyroid cancer. Many preclinical studies investigating the effects of inhibitors of the MAPK and PI3K pathways highlighted the importance of mutations in such signaling pathways and their impacts on the subsequent efficacy of targeted therapies, thus reinforcing the need of more personalized therapeutic strategies. Our review also points out the multiple possibilities of combinatory strategies, particularly using therapies targeting proliferation, survival, angiogenesis, and in combination with conventional treatments such as chemotherapies. In any case, resistances to anticancer therapies always develop through the activation of alternative signaling pathways. Combinatory treatments aim to blockade such mechanisms, which are gradually decrypted, thus offering new perspectives for the future. The preclinical and clinical aspects of our review allow us to have a global opinion of the different therapeutic options currently evaluated in combination and to be aware about new perspectives of treatment of thyroid cancer.

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“…Several anaplastic thyroid carcinomas carrying STRN-ALK have also been reported (Kelly et al 2014, Perot et al 2014, Godbert et al 2015. The role of STRN-ALK in the progression from PTC to PDTC thyroid carcinoma has been documented (Nikitski et al 2018). More recently, new fusion partners of ALK have been identified in thyroid cancer including TFG, GTF2IRD1, and CCDC149 (McFadden et al 2014, Landa et al 2016, Vanden Borre et al 2017.…”

Section: Introductionmentioning

confidence: 99%

Characterization of thyroid cancer driven by known and novel ALK fusions

Panebianco

Nikitski

Nikiforova

et al. 2019

Endocrine-Related Cancer

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ALK fusions are found in various tumors, including thyroid cancer, and serve as a diagnostic marker and therapeutic target. Spectrum and outcomes of ALK fusions found in thyroid nodules and cancer are not fully characterized. We report a series of 44 ALK-translocated thyroid neoplasms, including 31 identified preoperatively in thyroid fine-needle aspirates (FNA). The average patients’ age was 43 years (range, 8–76 years); only one with radiation history. All 19 resected thyroid nodules with ALK fusion identified preoperatively were malignant. Among nodules with known surgical pathology (n = 32), 84% were papillary thyroid carcinomas (PTCs) and 16% poorly differentiated thyroid carcinomas (PDTCs). PTCs showed infiltrative growth with follicular architecture seen exclusively (30%) or in combination with papillary and/or solid growth (37%). Tumor multifocality was seen in 10 (31%) PTC cases. Most PDTC had a well-differentiated PTC component. Lymph node metastases were identified in 10/18 (56%) patients with neck dissection. The most common ALK fusion partners were STRN (n = 22) and EML4 (n = 17). In five cases, novel ALK fusion partners were discovered. All five PDTCs carried STRN-ALK fusion. On follow-up, ten patients were free of disease at 2–108 months, whereas two patients with PDTC died of disease. In summary, ALK fusion-positive thyroid carcinomas are typically infiltrative PTC with common follicular growth, which may show tumor dedifferentiation associated with increased mortality. Compared to EML4-ALK, STRN-ALK may be more common in PDTC, and ~10% of ALK fusions occur to rare gene partners. When ALK fusion is detected preoperatively in FNA samples, malignancy should be expected.

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Mouse Model of Poorly Differentiated Thyroid Carcinoma Driven by STRN-ALK Fusion

Cited by 16 publications

References 60 publications

A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review

A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review

Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses

Characterization of thyroid cancer driven by known and novel ALK fusions

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