Early evolutionary divergence between papillary and anaplastic thyroid cancers

Capdevila, Jaume; Mayor, Regina; Mancuso, Francesco; Iglesias, Carmela; Caratù, Ginevra; Matos, Ignacio; Zafón, Carles; Hernando, Jorge; Petit, Audrey; Nuciforo, Paolo; Cameselle-Teijeiro, José; Álvarez, Clara; Recio, Juan A.; Tabernero, Josep; Matías‐Guiu, Xavier; Vivancos, Ana; Seoane, Joan

doi:10.1093/annonc/mdy123

Cited by 51 publications

(34 citation statements)

References 33 publications

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“…Additionally, many ATCs carry mutations, such as BRAF Val600Glu or NRAS Gln61Arg, that are signature mutations of WDTCs. A recent publication including 3 ATC/PTC pairs, however, challenged this school of thought by showing few shared mutations at high VAF and concluded that ATCs and WDTCs were likely evolutionarily largely independent . Our study explores this question in a relatively larger cohort and investigates the hypothesis more extensively through clonality‐based evolutionary analysis.…”

Section: Discussionsupporting

confidence: 94%

“…Although the coexistence of well‐differentiated and anaplastic tumors and their partly overlapping genetic profiles are suggestive of a genetic pathway of dedifferentiation of ATC from a well‐differentiated tumor, this hypothesized progression has not been extensively investigated with next‐generation sequencing approaches. A recent study of 3 paired ATCs and papillary thyroid carcinoma (PTCs) suggested early divergence of ATC and PTC and concluded that they were largely distinct entities . However, that study's small sample size and exclusion of follicular thyroid carcinomas (FTCs) restricts the generalizability of the conclusions, and methodological assumptions may obscure the overlapping mutational profiles of the 2 tumors.…”

Section: Introductionmentioning

confidence: 99%

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Clonal evolution analysis of paired anaplastic and well‐differentiated thyroid carcinomas reveals shared common ancestor

Dong

Nicolson

Choi

et al. 2018

Genes Chromosomes & Cancer

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Foci of papillary or follicular thyroid carcinoma are frequently noted in thyroidectomy specimens of anaplastic thyroid carcinoma (ATC). However, whether ATCs evolve from these co-existing well-differentiated thyroid carcinomas (WDTCs) has not been well-understood. To investigate the progression of ATC in patients with co-existing WDTCs, five ATC tumors with co-existing WDTCs and matching normal tissues were whole-exome sequenced. After mapping the somatic alteration landscape, evolutionary lineages were constructed by sub-clone analysis. Though each tumor harbored at least some unique private mutations, all five ATCs demonstrated numerous overlapping mutations with matched WDTCs. Clonal analysis further demonstrated that each ATC/WDTC pair shared a common ancestor, with some pairs diverging early in their evolution and others in which the ATC seems to arise directly from a sub-clone of the WDTC. Though the precise lineal relationship remains ambiguous, based on the genetic relationship, our study clearly suggests a shared origin of ATC and WDTC.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Clonal evolution analysis of paired anaplastic and well‐differentiated thyroid carcinomas reveals shared common ancestor

Dong

Nicolson

Choi

et al. 2018

Genes Chromosomes & Cancer

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“…Anaplastic thyroid cancer (ATC), accounting for 1-5% of all thyroid malignancies, is one of the most malignant endocrine tumors, with a patient median survival of less than 1 year [1]. ATC may arise de novo or by dedifferentiation of pre-existing well-differentiated thyroid tumors [2,3]. Deciphering its pathogenesis is likely to lead to the development of more effective therapy.…”

Section: Introductionmentioning

confidence: 99%

Global RNA Expression and DNA Methylation Patterns in Primary Anaplastic Thyroid Cancer

Ravi

Yang

Mylona

et al. 2020

Cancers

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Anaplastic thyroid cancer (ATC) is one of the most malignant tumors, with a median survival of only a few months. The tumorigenic processes of this disease have not yet been completely unraveled. Here, we report an mRNA expression and DNA methylation analysis of fourteen primary ATCs. ATCs clustered separately from normal thyroid tissue in unsupervised analyses, both by RNA expression and by DNA methylation. In expression analysis, enrichment of cell-cycle-related genes as well as downregulation of genes related to thyroid function were seen. Furthermore, ATC displayed a global hypomethylation of the genome but with hypermethylation of CpG islands. Notably, several cancer-related genes displayed a correlation between RNA expression and DNA methylation status, including MTOR, NOTCH1, and MAGI1. Furthermore, TSHR and SLC26A7, encoding the thyroid-stimulating hormone receptor and an iodine receptor highly expressed in normal thyroid, respectively, displayed low expression as well as aberrant gene body DNA methylation. This study is the largest investigation of global DNA methylation in ATC to date. It shows that aberrant DNA methylation is common in ATC and likely contributes to tumorigenesis in this disease. Future explorations of novel treatments should take this into consideration.Cancers 2020, 12, 680 2 of 11 to display promoter hypermethylation in ATC include PTEN, RAP1GAP, RASAL1, REC8, RASSF1,, whereas hypomethylation has been observed in NOTCH4, MAP17, and TCL1B. Notably, TSHR and NKX2-1 (previously TTF-1), involved in thyroid functions, have also been reported to be hypermethylated in ATC [17,18].Matched expression and methylation data may unravel genes that are dysregulated by methylation and that could contribute to tumorigenesis. However, no such studies have hitherto been performed on the genomic level in ATC. Here, we applied RNA sequencing (RNA-seq) and genome-wide methylation arrays, including 850,000 CpG sites, on primary ATC tumor samples to identify novel genes that exhibit significant methylation and expression correlation and to further delineate the tumorigenic process of ATC.

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“…Although recent improvements in treating PTC, for example surgery, radioiodine and endocrine therapy. PTC cells still showed occasional metastasis, loss of differentiation, anaplastic thyroid and high aggressiveness [4,5]. Hence, the elucidation of mechanism and novel targets of signaling involved in PTC oncogenesis are still required.…”

Section: Introductionmentioning

confidence: 99%

KIFC1 accelerates the proliferation, migration and invasion of papillary thyroid cancer cells via MAPK signaling

Nie¹,

Han²,

Wen³

et al. 2020

Preprint

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Kinesin family member C1 (KIFC1) acts as a kind of minus end-directed motorized protein and is considered as an oncogene of some cancer types. However, no studies have fully elucidated its biological activity and molecular mechanisms in papillary thyroid cancer (PTC). The study focused on reporting the overexpression of KIFC1 in cell lines and tissues of PTC. Moreover, clinicopathological features analysis showed that KIFC overexpression is significantly correlated with extrathyroidal invasion and lymph node metastasis. Knockdown of KIFC1 significantly reduced cell growth, migration and invasion in PTC cells, and concomitant increased levels of differentiation markers, such as Tg and Nis. Knockdown of KIFC1 markedly increased the expression level of epithelial cell marker (E-cadherin), and decreased the expression levels of epithelial-mesenchymal transition (EMT) related transcriptional factor N-cadherin, Snail and ZEB1. Further study revealed that knockdown of KIFC1 downregulated stemness markers ALDH2 and SOX2, and inhibited the MAPK signaling cascades and downstream signaling, including p-ERK, ERK, p-JNK, JNK, MMP2, and MMP9, which can affect the expression of the EMT associated factors. Taken together, we reported that KIFC1 might promoted the proliferation, migration and invasion of PTC cells and offer a candidate molecular target for therapeutic intervention.

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Early evolutionary divergence between papillary and anaplastic thyroid cancers

Abstract: ATC diverge from PTC early in tumour development and both tumour types evolve independently. Our work allows the understanding of the relationship between ATC and PTC facilitating the clinical management of these malignancies.

Cited by 51 publications

References 33 publications

Clonal evolution analysis of paired anaplastic and well‐differentiated thyroid carcinomas reveals shared common ancestor

Clonal evolution analysis of paired anaplastic and well‐differentiated thyroid carcinomas reveals shared common ancestor

Global RNA Expression and DNA Methylation Patterns in Primary Anaplastic Thyroid Cancer

KIFC1 accelerates the proliferation, migration and invasion of papillary thyroid cancer cells via MAPK signaling

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