Identification of insertions in PTEN and TP53 in anaplastic thyroid carcinoma with angiogenic brain metastasis

Sadow, Peter M.; Dias‐Santagata, Dora; Zheng, Zongli; Lin, Derrick T.; Le, Long P.; Nucera, Carmelo

doi:10.1530/erc-15-0198

Cited by 6 publications

(3 citation statements)

References 18 publications

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“…TP53-Mutations leading loss of function of the tumor suppressor and cell cycle regulator p53 were first described as a unique characteristic of thyroid cancer dedifferentiation with high prevalence (50-80%) in ATC [109][110][111] . Further analysis with mouse model generation and targeted next-generation sequencing have confirmed the correlation between TP53 alterations and worse pathological features of ATC 112,113 .…”

Section: Genetic Alterations and Pathways Deregulation Associated Witmentioning

confidence: 81%

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Coding Molecular Determinants of Thyroid Cancer Development and Progression

Valvo

Nucera

2019

Endocrinology and Metabolism Clinics of North America

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Thyroid cancer is the most common endocrine malignancy and its trends of incidence are the highest compared to other tumors. The characterization of the molecular pathways involved in thyroid cancer initiation and progression has made huge progress, underlining the essential role of determined signaling to promote specific features, including dedifferentiation, invasiveness, metastasis and drug resistance. The discovery of many genetic alterations that include point mutations, chromosome translocations, deletions, and copy-number gain has provided new exciting biological insights with translational/clinical applications. Furthermore, mechanisms of drug resistance involve role of pericytes and deregulation of pro-angiogenic molecules such as the tyrosine kinases (TKs) in the microenvironment. BRAF V600E-positive thyroid tumor growth is also influenced by the tumor microenvironment, which is in turn altered by the tumor itself, leading to abnormal extracellular matrix (ECM) deposition and activation of angiogenic pathways. Many of the processes involved in thyroid tumor growth and metastasis are mediated by signaling molecules downstream of BRAF V600E and activated TKs. Overall, understanding how molecular pathways interplay is one of the key-strategies to develop new therapeutic treatments and improve prognosis.

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Section: Genetic Alterations and Pathways Deregulation Associated Witmentioning

confidence: 81%

“…In human thyroid tumors the most common genetic alteration associated is somatic deletions of the PTEN gene (~5-25%) due to loss of heterozygosity (LOH) on chromosome 10 134,135 . PTEN frameshift mutations can occur in ATC 113 ; also, PTEN mutation are more frequent in ATC (15%) compared to PDTC 12 .…”

Section: Pi3k-akt Pathway Mutations and Deregulations-mentioning

confidence: 99%

Coding Molecular Determinants of Thyroid Cancer Development and Progression

Valvo

Nucera

2019

Endocrinology and Metabolism Clinics of North America

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“…[14][15][16][17] Recently, frameshift insertions in PTEN and TP53 has also been reported in metastatic brain lesions and primary tumors in patients with ATC. 18 ALK gene rearrangements have also been reported, and a significant tumor response with 90% tumor shrinkage was reported in a patient treated with crizotinib. 19 As seen in this patient, up to 30% to 35% patients with ATC have coexisting well-differentiated thyroid cancers, suggesting that ATC is the end result of "dedifferentiation" of an initially well-differentiated lesion.…”

Section: Discussionmentioning

confidence: 95%

Response to Targeted Therapy inBRAFMutant Anaplastic Thyroid Cancer

Agarwal

Wang

Wilson

et al. 2016

J Natl Compr Canc Netw

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Anaplastic thyroid cancer (ATC) is an aggressive uncommon malignancy with limited treatment. Traditional antineoplastic chemotherapy has not been successful in the management of metastatic ATC. As a result, the focus has shifted to the development of novel therapies for this disease. The availability of economical comprehensive genomic profiling (CGP) platforms with rapid turn-around to identify molecular aberrations in tumors that are potential therapeutic targets has increasingly changed the face of cancer therapy. Identification of targetable aberrations may help identify novel treatment options for ATC. Herein, we report our experience with a 47-year-old patient with metastatic ATC who experienced recurrent, progressive disease and rapid clinical deterioration despite surgery, radiation therapy, and treatment with 2 different chemotherapy regimens. She was found to have a BRAF V600E mutation on CGP, and was started on targeted therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib. After 2 months of treatment, she showed a clinical and radiologic response. The patient remained on this combination for 9 months until evidence of disease progression. Discontinuation of these drugs was associated with rapid tumor growth. Through this case we want to emphasize the importance of early molecular sequencing and identification of genetic aberrations in patients with ATC, and using that information to develop therapies for ATC, an aggressive malignancy with limited therapy and a poor outcome.

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Identification of prognostic signature with seven LncRNAs for papillary thyroid carcinoma

Guo

Pan

et al. 2022

Advances in Medical Sciences

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Identification of insertions in PTEN and TP53 in anaplastic thyroid carcinoma with angiogenic brain metastasis

Cited by 6 publications

References 18 publications

Coding Molecular Determinants of Thyroid Cancer Development and Progression

Coding Molecular Determinants of Thyroid Cancer Development and Progression

Response to Targeted Therapy inBRAFMutant Anaplastic Thyroid Cancer

Identification of prognostic signature with seven LncRNAs for papillary thyroid carcinoma

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